Molecular Functions Ntawm Ceruloplasmin hauv Metabolic Kab Mob Pathology Part 2

Fe tseem ceeb heev rau ntau yam haujlwm hauv lub cev, suav nrog DNA synthesis, gene qhia, thiab kev sib txuas ntawm hemoglobin thiab ntau yam enzymes. Kev tshawb fawb ntau ntxiv tau pom tias Fe metabolism tsis zoo ua rau cov tshuaj insulin tsis kam thiab rog.57,58

Muaj qhov sib txuas tsis sib xws ntawm cov noob qhia thiab kev nco. Cov kev tshawb fawb tau pom tias peb cov noob tuaj yeem cuam tshuam rau peb txoj kev txawj ntse thiab kev nco. Tsis tas li ntawd, peb tus cwj pwm thiab kev ua neej kuj tseem tuaj yeem cuam tshuam txog cov noob caj noob ces, yog li cuam tshuam rau peb lub peev xwm nco.

Ua ntej, cov noob yog lub hauv paus ntawm tib neeg kev txawj ntse thiab kev nco. Cov kev tshawb fawb tau pom tias qee cov noob muaj feem cuam tshuam txog kev tsim cov cim xeeb, khaws cia, thiab khaws cia. Piv txwv li, qee cov noob encode cov proteins uas pab cov paj hlwb txuas thiab khaws cov ntaub ntawv. Lwm cov noob cuam tshuam rau synaptic plasticity, uas yog lub peev xwm ntawm neural circuits hloov. Kev qhia theem thiab kev hloov pauv ntawm cov noob no ncaj qha cuam tshuam rau peb txoj kev txawj ntse thiab kev nco.

Qhov thib ob, peb tus cwj pwm thiab kev ua neej kuj tseem tuaj yeem cuam tshuam cov noob qhia thiab cuam tshuam rau peb txoj kev txawj ntse thiab kev nco. Piv txwv li, kev ua neej nyob xws li kev tawm dag zog, noj zaub mov, thiab kev pw tsaug zog tuaj yeem cuam tshuam cov noob caj noob ces. Kev tawm dag zog tuaj yeem tsis tsuas yog ua kom lub cev noj qab haus huv xwb tab sis kuj txhim kho kev txawj ntse. Cov khoom xyaw xws li antioxidants, vitamins, thiab minerals nyob rau hauv cov zaub mov tuaj yeem txhawb lub hlwb kev noj qab haus huv, yog li txhim kho kev nco. Kev pw tsaug zog txaus tuaj yeem pab lub hlwb tshem cov khib nyiab thiab tswj kev noj qab haus huv.

Tsis tas li ntawd, kev puas siab puas ntsws kuj tuaj yeem cuam tshuam kev nco. Cov kev tshawb fawb tau pom tias kev puas siab puas ntsws tsis zoo xws li kev ntxhov siab, kev nyuaj siab, thiab kev ntxhov siab tuaj yeem ua rau lub hlwb ua haujlwm, yog li cuam tshuam rau kev nco. Yog li ntawd, tswj kev xav thiab tswj tus cwj pwm zoo yog cov yuam sij los txhawb kev nco thiab kev txawj ntse.

Hauv cov ntsiab lus, peb cov noob caj noob ces, kev ua neej, thiab kev puas siab puas ntsws tuaj yeem cuam tshuam rau peb lub peev xwm kev txawj ntse thiab kev nco. Txoj kev ua neej zoo thiab kev xav, nrog rau kev tswj cov noob caj noob ces, tuaj yeem pab peb ua tiav kev nco thiab kev txawj ntse. Qhov no qhia tau hais tias peb yuav tsum txhim kho peb lub cim xeeb, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim tias nws muaj antioxidant, tiv thaiv kev mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidative thiab inflammatory teb nyob rau hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv. paj hlwb. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm muaj peev xwm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv qhov tshwm sim ntawm kev paub tsis meej thiab cov kab mob neurodegenerative.

Nyem paub txoj hauv kev los txhim kho lub hlwb

Fe hauv kev noj zaub mov yog tswj hwm los ntawm Fe3+, uas txo qis rau Fe2+ los ntawm duodenal cytochrome B (DcytB) nyob rau sab saum toj daim nyias nyias ntawm cov hnyuv epithelial hlwb thiab tom qab ntawd thauj los ntawm divalent hlau thauj khoom -1 (DMT1) los ntawm txoj hnyuv epithelial hlwb thiab los ntawm TF mus rau lub siab los ntawm portalvein ncig.59,60

Tom qab nkag mus rau hauv daim siab, Fe yog siv los ua ke Fe-muaj cov proteins, thiab cov seem oxidized.61 Raws li ferrous oxidase, CP plays lub luag haujlwm tseem ceeb hauv kev tswj hwm ntawm Fe tshuav nyiaj li cas hauv vivo.

Thetransmembrane thauj ntawm Fe hauv vivo yuav tsum muaj cov neeg nqa khoom tshwj xeeb, ferroportin (Fpn). CP-ferroportinsystem yog lub ntsiab lus tso tawm ntawm intracellular Fe.62 Txawm hais tias muaj ntau cov proteins koom nrog hauv kev nqus ntawm Fe, tib qhov kev lees paub tso zis ntawm Fe hauv lub cell yog CP-Fpn system.63 CP hauv ntshav oxidizes Fe{{4. }} toFe3+, uas tuaj yeem khi rau Fpn thiab tom qab ntawd thauj mus rau lub hom phiaj.

Tom qab endocytosis, Fe yog metabolized lossis khaws cia.62 Lub siab yog thawj lub cev tau txais Fe los ntawm txoj hnyuv, thiab nws tseem yog lub hom phiaj tseem ceeb ntawm Fe toxicity. Fe staining nyob rau hauv cov neeg mob uas muaj mob qog noj ntshav qhia tau hais tias ntau dhau Fe yog tso rau hauv cov ntaub so ntswg nontumor, 64 thiab kev qhia ntawm CP nyob rau hauv cov ntaub so ntswg nontumor yog ntau dua li cov ntaub so ntswg.

Fe deposition tshwm sim nyob rau hauv 60-95% ntawm epithelial parenchyma hlwb ntawm daim siab. Histology qhia tau hais tias Fe deposition txo qis los ntawm cov hlab ntsha portal mus rau qhov chaw lobular, thiab kev qhia ntawm CP kuj txo qis.

Qhov no qhia tau hais tias qhov kev qhia siab ntawm CP hauv Fe deposition yog cuam tshuam nrog kev koom tes ntawm CP hauv cov hlau oxidation.64 Ntxiv rau, Culevels hauv cov neeg uas muaj CP-tsis muaj cov noob thiab aceruloplasminemia yog ib txwm lossis txo qis, tab sis Fe metabolism yog qhov tsis zoo, thiab kev siv. Cov tshuaj Fe-chelating tuaj yeem ua lub luag haujlwm kho mob.65 Cov txiaj ntsig no qhia txog lub luag haujlwm tseem ceeb ntawm CP hauv cov txheej txheem ntawm Fe thauj.

Antioxidant Kev Ua Haujlwm

Cov txheej txheem antioxidant ntawm plasma CP yog cov haujlwm ntawm ferrous oxidase, cuprous oxidase, thiab glutathione peroxidase thiab nws lub peev xwm los khawb ROS. CP yog ib qho tseem ceeb antioxidant uas tuaj yeem hloov cov divalent Fe mus rau hauv cov tshuaj lom neeg tsawg trivalent Fe yam tsis tso ROS.

Nyob rau tib lub sijhawm, CP tuaj yeem siv ntxiv cov nyhuv antioxidant, txo cov hlau toxicity hauv vivo, thiab zam kev puas tsuaj thiab kev ua haujlwm tsis zoo hauv lub cev.66,67 Raws li thaum ntxov xyoo 1982, Goldstein thiab al68 pom tias cov concentrations ntawm CPin cov ntshav tuaj yeem cuam tshuam qhov txo qis. ntawm n-ferritin C tswj los ntawm xanthine oxidase, uas zoo ib yam li cov nyhuv scavenging ofsuperoxide dismutase (SOD) ntawm O2-.

Feem ntau, Fenton cov tshuaj tiv thaiv tuaj yeem tshwm sim nrog Fe2+ hauv H2O2 (Fe2++H2O2→Fe3++OH−+OH+), tab sis thaum muaj CP, Fe2+ tuaj yeem raug oxidized rau Fe{10}} los ntawm nws cov Fe oxidase kev ua, yog li Fenton cov tshuaj tiv thaiv tuaj yeem raug tshem tawm thiab cov nyhuv antioxidant tuaj yeem paub.69

Piv nrog rau cov nyhuv scavenging ntawm SOD ntawm cov dawb radicals, qhov cuam tshuam ntawm CP yog qhov tsis muaj zog, tab sis nws kuj yog tas li; Txawm nyob rau hauv cov ntaub ntawv ntawm denaturation ntawm cov protein, nws tseem tuav cov nyhuv ntawm kev tshem tawm dawb radicals.

Qhov tshwm sim no tuaj yeem yog qhov tshwm sim ntawm cov tshuaj tiv thaiv ncaj qha ntawm CP thiab O2-. Ob leeg CP thiab denatured CP tuaj yeem khi rau Cu2+ hauv cov ntshav thiab cov ntaub so ntswg, cuam tshuam lipid peroxide, thiab ua kom muaj zog erythrocyte hydrolysis induced los ntawm Cu2+.70 Tsis tas li ntawd, CP tuaj yeem txhawb kev tsim cov s- Nitroso glutathione (GSO).

Thaum ntxiv rau kab lis kev cai monocytes, CP tuaj yeem txhawb nqa qhov kev qhia ntawm inducible nitric oxide (NO) synthase.Physiologically, TSIS tuaj yeem hnov ​​​​mob nrog hydroxyl radicals (-OH) los tsim nitrous acid (HONO) thiab txo qhov kev puas tsuaj ntawm hydroxyl radicals rau cov ntaub so ntswg.71 Paradis et al72 ntseeg tias qhov kev cuam tshuam ncaj qha tuaj yeem muab kev tiv thaiv ntawm tes los ntawm kev tiv thaiv mercaptan los ntawm irreversible oxidation.

CP Gene Variants

CP gene variants tau pom thiab sib tham hauv ntau qhov kev tshawb fawb tsis ntev los no. Cov noob hloov pauv hauv CP tuaj yeem cuam tshuam qhov kev nthuav qhia ntawm CP.

Cov protein no tsim los ntawm cov noob caj noob ces tuaj yeem degrade tam sim tom qab tso tawm ntawm ER, thiab tseem tuaj yeem nyob hauv ER nrog cov qauv txawv txav, tab sis tsis muaj kev ua haujlwm ntawm lub cev, xws li tsis muaj peev xwm khi tooj liab atoms, tsis muaj oxidase, thiab lwm yam.73-75 Txog rau hnub tim. , 172 tus neeg mob ntawm CP gene variants tau tshaj tawm thoob ntiaj teb, thiab 56 tau suav tias yog kab mob; Feem ntau ntawm cov xwm txheej tshwm sim hauv Nyij Pooj, tsis muaj cov tsos mob tshwm sim xws li kev cuam tshuam ntawm cov paj hlwb thiab cov kab mob siab hlau hnyav.76

Nyob rau tib lub sijhawm, cov neeg mob heterozygous nrog tib qhov kev hloov pauv tuaj yeem lossis tsis muaj tsos mob, qhia tias tsis tiav kev nkag mus ntawm CP noob, thiab ib puag ncig thiab lwm yam caj ces yuav cuam tshuam rau CP cov haujlwm.

Corradini thiab al77 pom tias CP genevariants tej zaum yuav ua rau methemoglobinemia thiab hlau overload nyob rau hauv cov neeg mob uas tsis yog-alcoholic fatty liverdisease, tab sis Pelucchi thiab al78 pom tias variants tej zaum yuav txawv los ntawm lwm yam kev kho mob.

CP hauv Metabolic Disease

Kev sib raug zoo nrog hom 2 mob ntshav qab zib

Mob ntshav qab zib yog ib hom kab mob metabolic uas tshwm sim los ntawm cov ntshav qabzib siab. Cov neeg mob feem ntau muaj carbohydrate, rog, thiab protein metabolism tsis txaus vim insulin tsis txaus lossis (thiab) insulin tsis kam.79 Ntshav qab zib kuj yog ib qho kev sib kis thoob ntiaj teb. Raws li 2017 Cov Lus Qhia Suav rau Kev Tiv Thaiv thiab Kev Kho Mob Ntshav Qab Zib Hom 2, qhov tshwm sim ntawm ntshav qab zib hauv Suav teb tau nce los ntawm 0.67 hauv 1980 txog 10.4 hauv 2013.80

Kev hloov pauv tsis zoo hauv CP tau pom hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus (T2DM), thiab cov txiaj ntsig tsis sib xws. Chacko et al81 pom tias cov qib CP hauv cov ntshav tau nce siab hauv cov neeg mob T2DM, thiab qib CP hauv cov neeg mob uas muaj teeb meem yog siab dua cov neeg mob uas tsis muaj teeb meem. Nyob rau tib lub sijhawm, hauv cov pej xeem zoo sib xws, Sarkar thiab al82 tau qhia tias plasma CP thiab protein thiols txo qis, tab sis qib ntawm Cu2+ yog qhov txawv txav.

Cov kev tshawb fawb no txhua tus qhia txog kev sib txuas ntawm CP thiab ntshav qab zib: 83,84 mob ntshav qab zib yog txuam nrog kev txawv txav hauv kev mob, oxidation, thiab kab mob, thiab CP koom nrog cov kev txawv txav no.

Raws li thaum xaus ntawm lub xyoo pua 20th, Pickup thiab Crook tau hais tias, txawm hais tias lub cev tsis muaj zog tiv thaiv kab mob rov qab sai sai tom qab qhov kev tawm dag zog, ua kom lub cev tiv thaiv kab mob hauv lub cev, txhawb kev nyob ib puag ncig ntawm lub sijhawm ntev hyperglycemia, txhawb kev tiv thaiv insulin, rog, ntshav qab zib, thiab nws cov teeb meem.85

Txij thaum ntawd los, ntau cov kev tshawb fawb soj ntsuam tau pom tias ntshav qab zib feem ntau yog nrog los ntawm kev nce siab ntawm ntau yam inflammatory yam. Ntau qhov kev tshawb fawb soj ntsuam kab mob kis tau ntxiv tau lees paub tias ntau yam kev mob tshwm sim tuaj yeem kwv yees qhov tshwm sim ntawm ntshav qab zib. Kev mob tshwm sim feem ntau ua rau cov qauv thiab kev ua haujlwm ntawm cov hlwb endothelial thiab islet B hlwb thiab cov teeb liab hloov ntawm insulin receptors, uas cuam tshuam rau cov metabolism hauv qabzib thiab thaum kawg ua rau mob ntshav qab zib hom 2. 89–91 : kuv

CP yog ib qho mob hnyav-theem reactive protein; nws cov concentration hauv plasma nce ob-to peb-fold thaum kis kab mob lossis raug mob. CP plays lub luag hauj lwm txiav txim siab nyob rau hauv cov kev cai ntawm innate thiab tshwj xeeb immuneresponses, uas yog lub ntsiab Cheebtsam ntawm lub active tiv thaiv kab mob thiab muaj kev cuam tshuam cov kev tiv thaiv ntawm lub cev ntawm tib neeg lub cev.

Nws ntseeg tau hais tias CP yog ib qho tshuaj tiv thaiv kab mob uas inhibits kev tsim cov tshuaj phem thaum lub sij hawm o.92 Yog li ntawd, raws li qhov ua rau mob, CP tuaj yeem muab cov kev kuaj mob tshiab thiab kho mob rau cov ntshav qab zib, tab sis xav tau kev tshawb fawb ntxiv.Oxidative stress yog ib qho tseem ceeb. nyob rau hauv qhov tshwm sim thiab kev loj hlob ntawm T2DM.93 Nyob rau hauv ib tug physiological xeev, tib neeg lub cev muaj antioxidant tiv thaiv systems uas yuav tshem tawm oxidation ntau lawm, xws li ROS thiab reactivenitrogen hom (RNS).

Nrog rau cov tshuab no, oxidation ntau lawm yuav sib npaug ntau lawm thiab tshem tawm. Oxidativestress hais txog kev cuam tshuam ntawm qhov sib npaug uas ua rau cov nqaij mos thiab cov macromolecules lom xws li cov proteins thiab nucleic acids.94 Oxidative stress tuaj yeem ua rau muaj kev puas tsuaj ntawm islet B cell ua haujlwm thiab peripheral insulin tsis kam, inducediabetes, thiab tseem ua rau muaj teeb meem loj xws li ntshav qab zib neuropathy, 95 mob ntshav qab zib retinopathy, 96, thiab kab mob ntshav qab zib mellitus.97 Kev sim hauv vitro pom tias cov tshuaj tiv thaiv nonenzymatic glycation hauv hyperglycemiafragments deactivates CP, thiab tso tawm Cu2+ koom nrog Fenton cov tshuaj tiv thaiv los tsim ROS.

Nyob rau tib lub sijhawm, ROS tuaj yeem cuam tshuam CP dua los tsim lub voj voog tsis zoo.98 Shukla thiab al99 qhia tias tsis muaj Cuinduces ntau ROS ntau lawm los ntawm Haber-Weiss cov tshuaj tiv thaiv thiab Fenton cov tshuaj tiv thaiv hauv cov ntaub so ntswg aortic ntawm cov kab mob ntshav qab zib luav qauv; Qhov tshwm sim no tsis pom nyob hauv cov qauv luav uas tsis muaj ntshav qab zib.

Sarkar et al82 thiab Jeppuet al100 pom tias qib ntawm cov ntshav CP yog inversely proportional rau ceev cov ntshav qabzib nyob rau hauv cov neeg mob uas muaj T2DM.Qhov no yuav qhia tau hais tias, nyob rau hauv cov ntaub ntawv ntawm hyperglycemia, muaj zog oxidative kev nyuaj siab ua rau kom muaj zog ntawm kev hloov pauv hlau xws li Cu tso tawm. cov chaw cia khoom, uas muaj feem yuav koom nrog Fenton thiabHaber-Weiss cov tshuaj tiv thaiv los tsim ROS.82,100,101

Nyob rau hauv xyoo tas los no, nws tau pom tias cov kab mob (Cr, Zn, Fe, Se, Mg, Cu) muaj feem xyuam rau cov piam thaj hauv cov metabolism. Cov ntsiab lus ua haujlwm tseem ceeb hauv kev sib txuas, kev tso tawm, khaws cia, kev ua haujlwm ntawm insulin, thiab lub zog metabolism. .102 CP feem ntau koom nrog cov metabolism hauv Cu thiab Fe. Ntau cov kev tshawb fawb qhia tias cov neeg uas muaj T2DM tau nce qib ntawm Cu thiab Fe.82,101,103 Cov nyhuv redox ntawm Cu thiab Fe tau koom nrog hauv kev tsim cov ROS, uas yog ib qho ua rau mob ntshav qab zib.93.

Ntxiv nrog rau cov nyhuv redox, Cu kuj tuaj yeem cuam tshuam rau kev ua ntawm zinc (Zn). Vim tias Zn thiab Cu yog ib khub ntawm cov kab mob antagonistic, lawv sib tw rau tib lub cev muaj protein, metallothionein, thaum lub plab zom mov. Thaum theem ntawm Cu nce, nws yuav cuam tshuam rau kev nqus ntawm Zn, uas yuav ua rau poob Zn loj hauv lub cev; Qhov txo qis ntawm Zn yuav txhawb qhov tshwm sim ntawm ntshav qab zib mellitus.46,104 Ntxiv mus, Cu thiab qee cov Cu enzymes koom nrog hauv kev sib txuas ntawm cov protein tshwj xeeb rau ntawm qhov chaw ntawm pancreaticislet B hlwb, GIUT2, uas txhawb kev tsim cov tshuaj insulin.

Thaum lub cev luv luv ntawm Cu, cov synthesis ntawm GIUT2 protein tsis txaus, cuam tshuam rau kev tsim cov tshuaj insulin. Kev tso tawm ntawm insulin kuj tseem tswj hwm los ntawm lub hauv nruab nrab paj hlwb. Cu plays lub luag haujlwm tseem ceeb hauv kev tswj hwm kev ua haujlwm ruaj khov ntawm lub hauv paus system, thiab nws qhov tsis muaj peev xwm cuam tshuam rau cov paj hlwb thiab txo qis cov tshuaj insulin, yog li ua rau lossis ua rau mob ntshav qab zib ntau ntxiv.102

Lee et al thiab lwm yam kev tshawb fawb kuj pom tias thaum Cu2+ ua ke nrog tib neeg amylin (HA), qhov kev sib xyaw ua ke no tuaj yeem ua kom tsis muaj tshuaj lom tsis zoo ntawm HA thiab thaiv cov polymerization thiab apoptosis ntawm cov hlwb, qhia tias cov complex ntawm Cu{{1 }} thiab HA tuaj yeem tiv thaiv cov islet cells.105Kev tshawb fawb ntau ntxiv tau pom tias Fe overload tuaj yeem ua rau muaj kev pheej hmoo ntawm ntshav qab zib.

Fe deposition nyob rau hauv lub siab ua rau oxidative kev nyuaj siab, tsub kom apoptosis, txo cov kev qhia ntawm IRS2 thiab GIUT2 nyob rau hauv lub siab, ua rau insulin tsis kam, thiab nws thiaj li ua rau cov piam thaj tsis zoo metabolism.106 Ntxiv mus, Fe koom nrog rau kev sib txuas ntawm hemoglobin hauv vivo, thiab Fe deficiency tuaj yeem ua rau anoxia ntawm cov ntaub so ntswg pancreatic, uas tuaj yeem cuam tshuam cov synthesis thiab tso tawm ntawm insulin.107

Muaj ntau cov proteins koom nrog hauv Fe thauj, tsis yog CP nkaus xwb. Thaum CP ua haujlwm tsis zoo, lub cev muaj txiaj ntsig zoo rau Fe metabolism, tab sis CP koom nrog cov txheej txheem tseem ceeb ntawm Fe excretion.63,108Thaum CP tsis ua haujlwm, nws yuav ua rau Fe tsub zuj zuj hauv cov ntaub so ntswg thiab ua rau mob ntshav qab zib mellitus. Txhawm rau kawm txog cov txiaj ntsig ntawm teapolyphenols ntawm cov piam thaj metabolism hauv CP gene knockout nas, nws tau pom tias CP gene knockout nas raug kev txom nyem los ntawm insulin tsis kam thiab cov piam thaj tsis zoo metabolism yooj yim dua vim Fe overload.106

CP kuj tseem ua lub luag haujlwm tseem ceeb hauv kev mob ntshav qab zib. Nws tau raug pom tias cov ntshav CP tuaj yeem siv los ua tus kws tshaj lij ntawm hom 2 mob ntshav qab zib nephropathy.109 Qhov no yuav yog vim qhov nce ntawm oxidative kev nyuaj siab thiab kev hloov pauv oxidative ntawm cov lipoprotein tsawg muaj feem xyuam rau kev mob ntshav qab zib, 110 thiab CP tuaj yeem cuam tshuam. qib oxidation.98

Nws kuj tau pom tias qhov kev xaiv Cu2+-chelating tus neeg sawv cev trientine tuaj yeem ua rau muaj kev cuam tshuam ntawm ventricular ejection feem ntau thiab txo qis sab laug ventricular mass Performance index hauv cov neeg mob uas muaj T2DM nyuaj los ntawm sab laug ventricular hypertrophy. Qhov no qhia tau hais tias CP tuaj yeem txhim kho T2DM nrog rau sab laug ventricular hypertrophy, tab sis kev tshawb fawb soj ntsuam tseem xav tau los txheeb xyuas qhov kev xav no.111

Txhawm rau sau cov ntsiab lus ntawm cov ntshav qab zib retinopathy, peb pom tias CP, ua ib qho enzyme lom, ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob ntshav qab zib retinopathy.112Cov ntsiab lus, CP muaj kev sib raug zoo nrog kev tsim thiab kev loj hlob ntawm ntshav qab zib thiab tuaj yeem ua lub luag haujlwm tiv thaiv. cov piam thaj metabolism tsis zoo, muab cov kev tshawb fawb tshiab rau kev kuaj mob thiab kev kho mob ntshav qab zib.

Kev sib raug zoo nrog hyperlipidemia

Hyperlipidemia yog ib hom kab mob pathological ntawm lipid metabolism. Cov tsos mob tshwm sim yog nce qib ntawm cov roj cholesterol tag nrho (TC), triglyceride (TG), low-density lipoprotein (LDL), thiab txo qis ntawm cov ntshav lipoprotein (HDL).

Raws li kev tshawb fawb, tag nrho cov kab mob hyperlipidemia hauv cov neeg mob hnub nyoog tshaj 18 xyoo hauv Suav teb yog 40.40%; Kev nthuav dav ntawm LDL-C yog qhov siab tshaj plaws (33.9%), tom qab ntawd siab TG (13.1%).113 Kev tshawb fawb qhia tias ntawm 2010 thiab 2030 tus naj npawb ntawm cov neeg mob uas muaj kab mob plawv (CVDs) hauv Suav teb yuav nce 9.2million.114 Hyperlipidemia. muab faib ua thawj thiab theem nrab.

Primary hyperlipidemia muaj familialtendency.115 Secondary hyperlipidemia yog dyslipidemia tshwm sim los ntawm lwm yam kab mob, xws li ntshav qab zib thiab kub siab. Tsis tas li ntawd, hnub nyoog, qhov hnyav, thiab kev ua neej nyob, xws li kev noj haus, kev tawm dag zog, thiab kev ntxhov siab, tuaj yeem cuam tshuam rau cov ntshav lipid.

Tam sim no ntseeg tau tias cov txheej txheem pathological ntawm hyperlipidemia muaj feem cuam tshuam nrog endoplasmic reticulum (ER) kev ntxhov siab, genepolymorphism, inflammatory xeev, oxidative kev nyuaj siab, plab hnyuv, thiab kab kawm.116 Kev tshawb fawb tau pom tias CP cuam tshuam rau dyslipidemia thiab tuaj yeem koom nrog ntau theem ntawm hyperlipidemia.ER kev nyuaj siab plays lub luag haujlwm tseem ceeb hauv lipid metabolism thiab protein synthesis.117

Ntau yam physiological thiab pathological disturbances tuaj yeem cuam tshuam cov txheej txheem folding ntawm thawj cov proteins hluavtaws hauv ER kab noj hniav, ua rau kom nce andaccumulation ntawm unfolded thiab misfolded proteins, uas yog ER stress.118 SR-BI yog ib tug loj receptor rau HDL, thiab ERstress induces downregulation ntawm SR. -BI gene qhia, ua rau lipid metabolism tsis meej.119,120 GRP78 yog amolecular marker ntawm ER kev nyuaj siab.

Zhou et al121 pom tias mRNA thiab protein qhia ntawm GRP78 hauv hyperlipidemicrats tau txo qis, thiab, tom qab kev kho mob, ntshav TC, TG, thiab LDL-C tau txo qis, thiab GRP78 cov noob qhia thiab cov ntsiab lus protein tau nce ntxiv. Tag nrho cov kev tshawb fawb no tau qhia tias ER kev nyuaj siab playsan lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob hyperlipidemia.121

Cov kev tshawb fawb ntawm Cu-loaded hepatocytes kab lis kev cai hauv vitro qhia qhov tseem ceeb ER kev nyuaj siab hauv hepatocytes, yog li kev puas tsuaj rau Cu-loaded hepatocytes yog ze ze rau kev ntxhov siab ER ntau dhau.122Ntxiv mus, Kono thiab al123 pom tias cov tib neeg uas muaj aceruloplasminemia muaj ER kev nyuaj siab ua rau kev tuag ntawm tes.

Yog li, peb xav tias CP tuaj yeem zam kev ntxhov siab ER los ntawm kev nce qib Cu los ntawm kev tswj hwm Cu metabolism, yog li txo qhov tshwm sim ntawm hyperlipidemia. Txawm li cas los xij, kev tiv thaiv ntawm CP ntawm hyperlipidemia tseem yuav tsum tau lees paub los ntawm cov kev tshawb fawb cuam tshuam.

Nws yog tam sim no ntseeg hais tias cov inflammatory teb yog nrog los ntawm qhov tshwm sim thiab kev loj hlob ntawm hyperlipidemia, uas yuav ua rau kom lub tsub zuj zuj ntawm cov rog nyob rau hauv daim siab hlwb.

Kev sib sau ntawm cov rog txuas ntxiv ua rau cov kab mob ua rau muaj kev cuam tshuam hauv lub voj voog tsis zoo, ua rau muaj kev cuam tshuam lipid. Cov kev tshawb fawb tau pom tias qib ntawm cov teeb meem muaj feem cuam tshuam xws li C-reactive protein nyob rau hauv cov neeg mob hyperlipidemia yog qhov muaj txiaj ntsig zoo thiab muaj kev cuam tshuam zoo nrog TC, TG, thiab LDL-C.124 CP, raws li cov protein ua mob hnyav, tuaj yeem ua lub luag haujlwm hauv kwv yees qhov tshwm sim thiab prognosis ntawm hyperlipidemia. Lub luag haujlwm tseem ceeb ntawm CP hauv qhov mob yuav tsum tau kawm ntxiv.

Hauv cov neeg mob hyperlipidemia, qib ntawm oxidative kev nyuaj siab hauv vivo nce, thaum tag nrho cov antioxidant muaj peev xwm txo qis. Yog li ntawd, nws yog qhov zoo uas cov txheej txheem ntawm oxidative kev nyuaj siab koom nrog qhov tshwm sim ntawm lipidmetabolism txawv txav. Hydroxyl radicals, oxidative khoom, tuaj yeem cuam tshuam ncaj qha nrog lipids, inducing lipid peroxidation thiab ua rau kev puas tsuaj rau ntau yam biomolecular daim nyias nyias, 125,126 thaum kawg ua kom cov txheej txheem ntawm atherosclerosis thiab ua rau muaj kev pheej hmoo ntawm kab mob plawv.127

Raws li ib qho tseem ceeb antioxidant, CP muaj kev kho mob ntawm oxidative kev nyuaj siab hauv lub cev. Cov kev tshawb fawb tau pom tias CP tuaj yeem tshem tawm cov hydroxyl radicals thiab txhim kho cov lipid peroxidation xeev.128 Txawm li cas los xij, cov kev tshawb fawb tseem qhia tau tias oxidative kev nyuaj siab yuav hloov CP los ntawm kev tiv thaiv kab mob mus rau vascular pathological factor.129

Cov ntaub ntawv no tau pom tias CP, raws li nws cov qauv thiab kev ncaj ncees incombination nrog Cu, tuaj yeem ua lub luag haujlwm oxidant zoo hauv LDL ntau dua li muaj cov nyhuv antioxidant. Qhov no kuj ua pov thawj tias kev puas tsuaj ntawm kev sib xyaw ua ke no tuaj yeem hloov pauv cov tshuaj tiv thaiv antioxidant ntawm CP.130 Yog li ntawd, CP tuaj yeem muaj kev tiv thaiv thiab kwv yees cov txiaj ntsig ntawm hyperlipidemia, tab sis cov txheej txheem pathophysiological tsis tau kawm.

Kev sib raug zoo nrog Obesity

Kev rog rog yog ib hom kab mob metabolic uas feem ntau tshwm sim los ntawm kev sib cuam tshuam ntawm kev sib txuas ntawm caj ces, ib puag ncig, thiab lwm yam, xws li qhov hnyav nce los ntawm kev faib cov rog tsis zoo lossis muaj roj ntau hauv lub cev. Kev rog dhau tuaj yeem ua rau muaj ntau yam teeb meem thiab muaj feem cuam tshuam rau qhov tshwm sim ntawm ntau yam mob thiab mob ntev thiab cov tsos mob, xws li dyslipidemia, metabolic syndrome, T2DM, atherosclerosis, thiab CVD.

Raws li kev tshawb fawb xyoo 2015, kev rog thiab rog rog ntawm cov menyuam yaus hnub nyoog 6 txog 17 xyoo hauv Suav teb tau nce mus txog 6.4% thiab 9.6%, feem, uas yog 5.1 thiab 4.3 feem pua ​​​​ntawm cov ntsiab lus siab dua feem pua ​​​​hauv 2002.131,132 Txoj kev tshawb fawb pom tias CP cuam tshuam nrog kev rog rog. , thiab Tajik li al pom qhov txo qis hauv plasma CP qib hauv cov poj niam rog tom qab poob phaus los ntawm kev noj haus.133

CP tuaj yeem koom nrog hauv cov lus teb inflammatory thiab oxidative kev ntxhov siab hauv qhov tshwm sim thiab kev loj hlob ntawm kev rog, thiab nws kuj tuaj yeem cuam tshuam kev rog los ntawm kev tswj cov hnyuv thiab cov teeb meem. Kev tshawb fawb tam sim no qhia tias kev rog rog yog qhov mob qis qis uas tshwm sim los ntawm kev sib cuam tshuam ntawm adipocytes, macrophages. , thiab lwm lub cev tiv thaiv kab mob uas permeate thiab dilate cov ntaub so ntswg adipose.

Kev loj hlob ntawm kev rog rog ua rau adipocytes hypertrophy, uas yog cov neeg sawv cev tshaj plaws ntawm cov ntaub so ntswg ua haujlwm tsis zoo, thiab cov yam ntxwv no ua rau muaj kev tsim cov proinflammatory cytokines.134 CP, raws li qhov ua rau mob, tuaj yeem siv los ntsuas cov qib ntawm o thiab paub qhov txawv ntawm cov kab mob. . Kim et al,8 siv cov txheej txheem proteindifferential zaub, pom tias kev nce hauv CP yog cuam tshuam nrog kev rog, qhia tias CP tuaj yeem siv los ua biomarker ntawm kev rog.

Tsis tas li ntawd, piv nrog fibrinogen, C-reactive protein (CRP), thiab IL-6, CP yog qhov zoo dua qhov kev kwv yees ntev ntev rau kev rog rog.135 Txawm li cas los xij, seb CP plays lub luag haujlwm tseem ceeb hauv kev sib haum xeeb inducing lub luag haujlwm hauv kev rog rog, seb nws qhov kev nce ntxiv tuaj yeem cuam tshuam qhov xwm txheej ntawm kev rog rog, lossis txawm tias itis tsuas yog tus cim yooj yim tseem xav tau kev tshawb fawb.

Ntau cov kev tshawb fawb tau pom tias qib ntawm oxidative kev nyuaj siab nyob rau hauv cov neeg mob rog rog yog nce rau ntau yam, uas mitochondrial kev hloov pauv ua lub luag haujlwm txiav txim siab. Mitochondrial dysfunction ntawm cov ntaub so ntswg adipose nyob rau hauv cov neeg mob uas rog rog yog tus cwj pwm los ntawm kev txo qis mitochondrial biosynthesis thiab kev ua haujlwm, ntau ntau ROS, thiab nce autophagy.136-138.

Tag nrho cov xwm txheej no tuaj yeem cuam tshuam rau cov ntaub so ntswg adipose. CP tuaj yeem txhawb cov metabolism los ntawm kev tswj cov metabolism hauv Cu thiab Fe, txhawb nqa mitochondrial biosynthesis thiab kev ua ub no, txhim kho oxidative kev nyuaj siab hauv adipositis, thiab inhibiting autophagy.139 Kev tshawb fawb tau pom tias cov hnyuv muaj feem cuam tshuam rau hauv cov txheej txheem metabolic ntawm tib neeg noj zaub mov thiab lub zog.

Cov kab mob hauv plab tuaj yeem kho qhov tshwm sim thiab kev loj hlob ntawm kev rog rog tsis tsuas yog cuam tshuam rau kev nqus ntawm lub zog metabolism thiab lub plab hnyuv permeability tab sis kuj los ntawm kev koom tes hauv cov txheej txheem metabolic ntawm lub cev thiab cuam tshuam nrog tib neeg cov ntaub so ntswg thiab kab mob.140 Cov kab mob ntawm cov kab mob xws li Cu thiab Fe kuj tuaj yeem cuam tshuam rau cov muaj pes tsawg leeg thiab kev ua haujlwm ntawm cov hnyuv, nrog rau kev ua haujlwm ntawm lipid metabolism.141,142 Txawm li cas los xij, lub luag haujlwm ntawm CP intestinal flora tseem tsis to taub.

Lub Ntiaj Teb Cancer Research Fund tau xaus rau xyoo 2007 tias kev rog rog yog txuam nrog kev pheej hmoo siab ntawm pancreatic (postmenopausal) lub mis, endometrial, thiab raum mob cancer.143 Ib txoj kev tshawb nrhiav pom tias CP yog ib qho tshiab adipokine nrog nce kev nthuav tawm hauv cov ntaub so ntswg adipose ntawm cov rog rog thiab cov hlwb. ntawm obesity-related cancers.144

Txawm hais tias muaj kev sib raug zoo ntawm overexpression ntawm CP thiab mob qog noj ntshav hauv cov neeg mob rog rog tseem xav tau kev tshawb fawb ntxiv.Thaum Safavi thiab al145 tau soj ntsuam kev sib raug zoo ntawm qib CP thiab kev rog rog, lawv pom tias tsis muaj kev sib raug zoo, tab sis cov qib CP tau zoo sib xws. nrog ntshav triglyceride. Kev sib raug zoo ntawm CPand rog tseem xav tau kev tshawb fawb ntau.

Kev sib raug zoo nrog Lwm Cov Kab Mob Metabolic

Ntxiv nrog rau ntshav qab zib thiab rog rog, CP tseem cuam tshuam nrog lwm cov kab mob metabolic, xws li kab mob plawv (CHD). Göçmen et al146 pom tias qib CP nce hauv cov neeg mob CHD. Hauv lawv txoj kev tshawb fawb, lawv pom tias qib CP yog qhov tsis txaus ntseeg muaj feem cuam tshuam rau CVD.146 Mori thiab al147 cais qhov kev pheej hmoo los ntawm CP los ntawm qhov mob ( 1-antitrypsin, 1-acid glycoprotein, {{5} }macroglobulin, haptoglobin, fibrinogen, C4b binding protein, lipoprotein, thiab CRP) thiab qhia tias CP tuaj yeem ua tus muaj kev pheej hmoo txaus ntshai rau coronary atherosclerosis thiab ua tus cim rau cov kab mob no.147

Ntau qhov kev tshawb fawb tau pom muaj kev sib koom ua ke ntawm CP thiab CHD, tab sis tsis tau mus txog qhov kev txiav txim siab txog cov txheej txheem rau lub luag haujlwm ntawm CP hauv CHD. Qee cov kev tshawb fawb tau qhia tias oxidation ntawm LDLleads rau qhov pib lossis nrawm ntawm cov txheej txheem ntawm atherosclerosis, thiab CP yog ib qho zoo rau kev oxidation ntawm LDL. CP, los ntawm kev cuam tshuam tsis muaj qib, tuaj yeem txo qhov bioavailability ntawm NO hauv plasma, inhibiting nws cov kev tiv thaiv ntawm lub plawv ischemia thiab tsis ua haujlwm.

Txawm li cas los xij, tseem muaj cov kev tshawb fawb qhia tias CP yog ib qho antioxidant uas ua lub luag haujlwm tiv thaiv kev loj hlob ntawm CHD. Rau kev soj ntsuam zoo dua ntawm kev ua tiav ntawm lub luag haujlwm ntawm CP hauv CVD tau sau los ntawm cov kev tshawb fawb soj ntsuam, peb qhia luv luv cov ntsiab lus tseem ceeb ntawm kev tshawb fawb hauv xyoo tas los no, raws li qhia hauv Table 1. Txhawm rau tshawb nrhiav cov kev tshawb fawb tshiab, Web of Science tau siv los khaws CP cov kev tshawb fawb luam tawm los ntawm 2016 txog 2020. Cov kev tshawb fawb tau tshaj tawm 2098 thawj cov kev tshawb fawb thiab kev tshuaj xyuas, uas tau xa tawm mus rau CiteSpace rau kev soj ntsuam tawg, raws li pom hauv daim duab 5.Raws li tau pom, kev tshawb fawb ntawm CP hauv tsib xyoos dhau los tau tsom mus rau hauv vitro thwmsim, tshuaj tiv thaiv oxidation. , tiv thaiv kab mob, thiab kab mob metabolic. Ntxiv mus, txij li xyoo 2018, kev tshawb fawb txog kev tiv thaiv kab mob thiab ntshav qab zib tau dhau los ua lub ntsiab lus kub thiab muaj txiaj ntsig rau CP.

Tam sim no, kev koom tes ntawm CP thiab cov kab mob metabolic xws li ntshav qab zib tau pom, thiab nws ntseeg tias CP feem ntau ua lub luag haujlwm hauv cov kab mob los ntawm kev tswj cov tooj liab thiab hlau metabolism, oxidative kev nyuaj siab, thiab mob. tooj liab thiab hlau tau raug kawm kom huv si, cov lus nug tseem nyob.Puas yog CP feem ntau ua haujlwm ua antioxidant lossis oxidant hauv oxidative kev nyuaj siab? Nws puas ua lub luag haujlwm tiv thaiv kab mob hauv cov lus teb inflammatory?

Vim li cas cov kev tshawb fawb ntawm CP, siv cov kev tshawb fawb sib txawv ntawm cov tib neeg zoo sib xws, pom cov txiaj ntsig sib txawv lossis qhov sib txawv ntawm kev tshawb fawb? Tsis tas li ntawd, kev ruaj ntseg ntawm CP's physiological functions tsis tau txiav txim siab. Yog li ntawd, kev tshawb fawb yav tom ntej yuav kawm txog cov txheej txheem ntawm CP hauv cov kab mob metabolic, tshwj xeeb tshaj yog nws txoj kev koom tes inoxidative kev nyuaj siab thiab kev tiv thaiv kab mob los nthuav tawm qhov tshwj xeeb txuas ntawm CP thiab cov kab mob metabolic thiab nrhiav lub hom phiaj meej. rau nws txoj haujlwm.

Xaus

Kev tshawb fawb ntau ntxiv tau pom muaj kev sib raug zoo ntawm CP thiab cov kab mob metabolic xws li ntshav qab zib thiab hyperlipidemia thiab tau pom tias CP tuaj yeem koom nrog cov txheej txheem physiological thiab pathological ntawm cov kab mob no.

Ntau qhov kev tshawb fawb tau pom tias CP ua lub luag haujlwm tseem ceeb hauv kev sib npaug ntawm Cu thiab Fe los ntawm nws cov haujlwm oxidase. CP nthuav tawm cov haujlwm antioxidant thiab tuaj yeem tiv thaiv cov ntaub so ntswg los ntawm kev puas tsuaj oxidative. Txoj kev tshawb nrhiav pom tias qib ntawm CP nce hauv lub xeev inflammatory, thiab txo qis kev ua kom cov neutrophils, qhia tias CP tuaj yeem siv los ua tus kws tshaj lij thiab antagonist ntawm o.66

Tam sim no, nws ntseeg tau tias CP ua lub luag haujlwm tiv thaiv kab mob hauv cov kab mob metabolic, feem ntau los ntawm kev koom nrog oxidative kev nyuaj siab thiab cov metabolism hauv Cu thiab Fe, thiab ua raws li cov kab mob inflammatory los kwv yees cov kab mob. Txawm li cas los xij, qee qhov kev tshawb fawb kuj tau pom tias CP ua lub luag haujlwm ntawm cov tshuaj antioxidant. Kev sib raug zoo ntawm CP thiab cov kab mob metabolic hauv tib neeg lub cev tsis meej. Txawm hais tias muaj ntau cov kev tshawb fawb tau pom muaj kev sib raug zoo ntawm CP thiab cov kab mob metabolic, kev tshawb fawb yav tom ntej yuav tsum tsom mus rau kev daws cov txheej txheem molecular ntawm CP hauv cov kab mob metabolic thiab kawm txog nws cov luag haujlwm.

Nqe lus ntawm Ethics

Kab lus no tsis muaj kev tshawb fawb nrog tib neeg lossis tsiaj ua los ntawm ib tus kws sau ntawv.

Kev lees paub

Peb xav ua tsaug rau cov kws tshawb fawb txog lawv txoj kev koom tes. Daim ntawv no tau txais kev txhawb nqa los ntawm Clinical Research Plan of SHDC (No. SHDC2020CR3028A thiab No. SHDC12019X16).

Sau Kev Pab Txhawb

Txhua tus kws sau ntawv tau muaj txiaj ntsig zoo rau kev ua haujlwm tau tshaj tawm, txawm hais tias yog nyob rau hauv kev xav, kev kawm tsim, kev ua tiav, nrhiav tau cov ntaub ntawv, kev tshuaj xyuas, thiab kev txhais lus, lossis tag nrho cov cheeb tsam no; koom nrog hauv kev sau ntawv, kho, lossis tshuaj xyuas cov kab lus; muab kev pom zoo zaum kawg ntawm cov ntawv luam tawm; tau pom zoo rau hauv phau ntawv journal uas tau xa tuaj; thiab pom zoo kom lav ris rau txhua yam ntawm txoj haujlwm.

Qhia tawm

Cov kws sau ntawv tshaj tawm tsis muaj qhov tsis sib haum xeeb ntawm kev txaus siab hauv txoj haujlwm no.

Cov ntaub ntawv

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