Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Cov Txheej Txheem Ntawm Copper Ions Thiab Lub Raum Fibrosis hauv 2023

Mob raum mob (CKD) yog lub raum tsis zoo los yog kev ua haujlwm los ntawm ntau yam ua rau ntau dua lossis sib npaug li 3 lub hlis. Txawm li cas los xij, CKD yog tus cwj pwm los ntawm kev loj hlob ntawm nephron poob, microvascular puas, txo cov peev xwm rov tsim dua tshiab, o, oxidative kev nyuaj siab, thiab kev hloov pauv hauv metabolic, thaum kawg ua rau lub raum tsis ua haujlwm thiab cov kab mob hauv lub raum kawg. Kev tshawb fawb txog kab mob kis tau pom tias txij li xyoo 1990 txog rau xyoo 2019, qhov tshwm sim ntawm CKD tau nce ntau ntawm 6.7% mus rau 10.6%. Ntawm lawv, 10% mus rau 15% ntawm cov neeg mob CKD tau nce mus rau theem kawg ntawm lub raum kab mob thiab xav tau kev kho mob rau lub neej, uas ua rau muaj kev puas tsuaj loj rau tib neeg thiab tsev neeg. Nqa lub nra hnyav [1-2]. Lub raum fibrosis yog ib hom kab mob pathological thiab qhov kawg tshwm sim ntawm CKD. Nws cov yam ntxwv morphological muaj xws li glomerulosclerosis, lub raum tubular atrophy, interstitial chronic o, thiab caws pliav. Nws yog tshwm sim los ntawm ntau deposition ntawm extracellular matrix Cheebtsam nrog rau collagen. Rau [2~3]. Kev tshawb fawb ntawm lub raum fibrosis yeej ib txwm yog qhov chaw kub hauv kev tshawb fawb CKD, thiab ntau dua 50% ntawm kev tshawb fawb txhua xyoo tsom mus rau lub raum fibrosis.

Nyem rau Cistanche rau mob raum

Tooj liab yog ib qho tseem ceeb ntawm cov kab hlau rau cov kab mob. Raws li cov cofactor lossis cov qauv ntawm cov enzymes, nws koom nrog ntau yam haujlwm hauv lub neej xws li cell-free radical scavenging, connective tissue synthesis, pigment formation, immune regulation, and neuromedin synthesis [4 ~ 5]. Tooj liab muaj nruj nqus, faib, thiab metabolism hauv lub cev. Extracellular tooj liab ions muaj nyob rau hauv daim ntawv ntawm Cu (II) thiab tuaj yeem khi ncaj qha mus rau divalent hlau thauj khoom 1, tab sis cov tooj liab ions tsis tuaj yeem siv ncaj qha los ntawm cov hlwb [6]. Nws yog feem ntau ntseeg hais tias ntau hom cell muaj xws li tooj liab uptake txoj kev. Ob lub reductases ntawm tib neeg prostate 6-transmembrane epithelial antigens 2 thiab 3 yog lub luag hauj lwm rau txo Cu (II) nyob rau saum npoo ntawm mammalian hlwb rau Cu (I). ) [7]. Tom qab ntawd, Cu(Ⅰ) tuaj yeem khi rau tooj liab thauj khoom 1 (CTR1) thiab xa mus rau hauv lub cell.

Peb lub ntsiab proteins thauj tooj liab ions mus rau subcellular organelles: (1) Superoxide dismutase 1 tooj liab chaperone, uas tuaj yeem xa tooj liab rau SOD1. (2) Cytochrome c oxidase tooj liab chaperone (COX17), shuttles ntawm cytoplasm thiab mitochondria, thauj tooj liab mus rau cytochrome oxidase nyob rau hauv ob txoj kev; ib tug thauj tooj liab ions mus rau cytochrome oxidase uas ploj lawm proteins 1 los yog 2, ob leeg proteins nyob rau hauv lub puab membrane ntawm mitochondria, thiab lawv hloov tooj liab ions mus rau tooj liab A site ntawm cytochrome c oxidase subunit 2; lwm qhov yuav hloov mus rau cytochrome c oxidase los ua ke protein, cytochrome c Cov oxidase sib dhos protein tuaj yeem xa cov tooj liab ions mus rau tooj liab B site ntawm cytochrome c oxidase subunit 1 [8]. Cov kev tshawb fawb tau tshaj tawm tias cov protein uas thauj cov tooj liab ions los ntawm cytoplasm mus rau mitochondria yog ib qho tsis paub txog tooj liab anion protein [9]. (3) Copper transporter antioxidant protein 1 tuaj yeem tau txais tooj liab ions xa los ntawm CTR1 thiab thauj mus rau Golgi. Cov tooj liab ions nkag mus rau Golgi ces muab tooj liab rau cov tooj liab enzymes nyob hauv Golgi los ntawm tooj liab ion thauj ATPase peptide thiab tooj liab ion thauj ATPase peptide, feem ntau suav nrog tyrosinase [10] thiab superoxide dismutase 3 [11], LOX[12] , thiab lwm yam. Thaum muaj ntau cov tooj liab ions hauv lub xov tooj ntawm tes, tooj liab ion thauj ATPase peptide / tooj liab ion thauj ATPase peptide tuaj yeem hloov mus rau hauv cov cell membrane kom tshem tawm cov tooj liab ntau dhau ntawm lub xov tooj ntawm tes thiab tswj cov tooj liab hauv lub cev [13].

Tooj liab ions muaj feem xyuam rau qhov tshwm sim thiab kev loj hlob ntawm fibrosis nyob rau hauv ntau yam kabmob. Hauv ntau qhov sib txawv ntawm lub cev fibrosis, cov ntaub so ntswg tooj liab ions tau nce. Wang et al. pom tias tooj liab ion overload ua rau tiam ntawm mitochondrial reactive oxygen hom, txhawb fibrosis ntsig txog noob qhia thiab myofibroblast sib txawv [14]. Copper tsub zuj zuj nyob rau hauv cardiomyocyte mitochondria induces mitochondrial puas, cytochrome c tso, thiab cell apoptosis, uas ntxiv ua rau mob plawv thiab aggravates cardiac fibrosis [15]. Hauv Wilson tus kab mob, tooj liab ions sib sau ua ke hauv mitochondria. Thaum siv tooj liab chelators penicillamine lossis methanectin, cov qauv mitochondrial thiab kev ua haujlwm tau zoo dua qub, thiab daim siab fibrosis tau txo qis [16]. Plasma tooj liab ions tau nce ntxiv hauv cov neeg mob lub raum tsis ua haujlwm, qhia tias tooj liab ions sib sau ua ke rau qee yam hauv lub cev thaum lub raum ua haujlwm tsis zoo [17]. Ib yam li ntawd, nyob rau hauv tus qauv nas ntshav qab zib, kev siv cov kev xaiv divalent tooj liab ion chelators tuaj yeem cuam tshuam qhov ua kom tsis zoo ntawm kev hloov pauv kev loj hlob 1 (TGF- 1) thiab txhim kho lub raum fibrosis [18]. Txawm li cas los xij, cov txheej txheem uas tooj liab ions ua rau lub raum ua haujlwm puas tsuaj thiab lub raum fibrosis tsis paub.

Kev tshawb fawb ntawm peb pawg neeg tshawb fawb feem ntau tsom rau lub luag haujlwm ntawm tooj liab ions thiab lawv txoj kev cuam tshuam hauv lub raum fibrosis. Cov kev tshawb fawb yav dhau los tau pom tias cov ntshav plasma tooj liab ions nce ntau hauv cov neeg mob lub raum tsis ua haujlwm, qhia tias tooj liab ions sib sau ua ke rau qee yam hauv lub cev thaum lub raum ua haujlwm tsis zoo [17]. Peb tau ua qhov kev tshawb nrhiav ua ntej rau hauv qhov no. Peb pom tias nyob rau hauv cov qauv nas ntawm lub raum fibrosis tshwm sim los ntawm unilateral ureteral obstruction, cov ntsiab lus tooj liab nyob rau hauv lub raum cov ntaub so ntswg yog ho nce; Kev nthuav qhia ntawm CTR1 tau nce hauv ob qho tib si fibrosis qauv thiab raum cov ntaub so ntswg ntawm cov neeg mob raum fibrosis. Cov txiaj ntsig zoo sib xws tau pom hauv TGF- 1- kho lub raum tubular epithelial hlwb thiab fibroblasts. Mechanistically, upregulation ntawm CTR1 cia siab rau TGF- 1-Smad3 signaling txoj kev, thiab cov txiaj ntsig ntawm chromatin immunoprecipitation kuj tau ua pov thawj tias Smad tuaj yeem khi rau tus txhawb nqa ntawm CTR1 hauv lub raum fibroblasts. Qhov siab CTR1 ua rau muaj kev nce ntxiv hauv cov cell ntawm tooj liab. Nce intracellular tooj liab ions qhib lysyl oxidase (LOX) los txhim kho kev sib txuas ntawm collagen thiab elastin, yog li txhawb lub raum fibrosis. Siv cov tooj liab ion chelator ammonium tetrathiomolybdate los yog down-regulating CTR1 kom txo tau intracellular tooj liab ions tuaj yeem txhim kho lub raum fibrosis induced los ntawm unilateral ureteral obstruction thiab inhibit qhov ua kom lub raum fibroblasts induced los ntawm TGF- 1. Nyob rau hauv cov ntsiab lus, intracellular tooj liab tsub zuj zuj activates LOX thiab txhawb cross-linking ntawm collagen thiab elastin, ua rau kom lub raum fibrosis. Inhibiting intracellular tooj liab overload yuav yog ib txoj hauv kev los txo lub raum fibrosis [5]. Txawm li cas los xij, hauv lub raum fibrosis, kev faib ntawm cov tooj liab ions hauv lub cev tsis paub meej.

Thaum Lub Peb Hlis 17, 2022, tus kws tshawb fawb tau luam tawm cov ntawv tshawb fawb txog tooj liab tuag nyob rau hauv cov ntawv xov xwm thoob ntiaj teb kev kawm Science [19]. Txoj kev tshawb no tau lees paub hauv tib neeg lub hlwb tias tooj liab-dependent cell tuag yog hom tshiab ntawm cell tuag uas txawv ntawm kev paub txog kev tuag ntawm tes. Thaum paub txog txoj kev tuag ntawm tes (xws li apoptosis, pyroptosis, ferroptosis) raug thaiv, necrosis, thiab lwm yam), tooj liab ions tseem tuaj yeem ua rau tuag ntawm tes. Pab neeg tshawb fawb hu ua hom kev tuag ntawm tes - tooj liab tuag. Pab neeg tshawb fawb ntxiv tau nthuav tawm cov txheej txheem ntawm tooj liab tuag. Qhov tooj liab-dependent cell tuag no tshwm sim los ntawm kev sib txuas ncaj qha ntawm tooj liab ions rau fatty acylated Cheebtsam nyob rau hauv lub tricarboxylic acid voj voog nyob rau hauv mitochondrial respiration, ua rau lub aggregation ntawm fatty acylated proteins thiab tom qab cov hlau-sulfur pawg proteins yog down-regulated, ua rau proteotoxic. kev nyuaj siab thiab thaum kawg ntawm tes tuag.

Mitochondria tsis yog ib qho tseem ceeb ntawm tooj liab reservoirs, tab sis kuj yog lub ntsiab tooj liab-siv organelles nyob rau hauv lub cell. Vim hais tias lub raum tubular hlwb xav tau ntau npaum li cas ntawm ATP los tswj lub cev kua thiab acid-base tshuav nyiaj li cas. Yog li ntawd, lub raum yog nplua nuj nyob rau hauv mitochondria. Cov kev tshawb fawb yav dhau los tau pom tias apoptotic tubular epithelial hlwb tuaj yeem txhawb lub raum fibrosis los ntawm paracrine profibrotic yam lossis kev tiv thaiv kab mob. Apoptosis tau muab faib ua txoj hauv kev endogenous thiab exogenous, thiab mitochondria ua lub luag haujlwm tseem ceeb hauv cov txheej txheem endogenous apoptosis ntawm cov hlwb. Kev sib raug zoo ntawm tooj liab overload nyob rau hauv mitochondria ntawm lub raum tubular epithelial hlwb thiab mitochondrial muaj nuj nqi, cell apoptosis, thiab lub raum fibrosis tsis tau qhia. Lub luag haujlwm thiab kev tswj hwm txoj cai ntawm tooj liab homeostasis hauv mitochondria yuav tsum tau piav qhia.

Peb qhov kev tshawb fawb tshaj tawm tshiab tshaj tawm ua pov thawj tias tooj liab ion tsub zuj zuj cuam tshuam rau kev ua haujlwm ntawm mitochondrial respiratory chain complex IV, ua rau lub cev puas tsuaj thiab ua rau lub raum mob hnyav [20]. Mitochondrial qauv tuaj yeem txhim kho tom qab kho nrog TM chelators. Txoj kev tshawb no tsom mus rau mitochondrial kev puas tsuaj kho los ntawm tooj liab ion overload hauv mitochondria, elucidating cov txheej txheem tshwj xeeb los ntawm kev sib sau ntawm tooj liab ions hauv mitochondria nyob rau hauv cov xwm txheej fibrotic koom nrog hauv mitochondrial cov qauv thiab kev ua haujlwm puas, cell apoptosis, thiab lub raum fibrosis los ntawm inhibiting kev ua ntawm respiratory. chain complex IV. Molecular mechanisms. Nyob rau tib lub sijhawm, txoj kev tshawb fawb no tshawb txog lub luag haujlwm tseem ceeb ntawm cov copper transporter COX17 hauv kev txo qis intramitochondrial overload thiab nthuav dav kev nkag siab txog kev them nyiaj thaum ntxov ntawm lub raum fibrosis.

Txawm hais tias muaj zog tooj liab ions tuaj yeem ua rau cov ntaub ntawv sib txawv thiab sib txawv ntawm cov cell puas, nws tsim nyog sau cia tias cov kev tshawb fawb tau ua pov thawj tias cov cellular tooj liab tuag tuaj yeem txo cov kab mob ntsws los ntawm inhibiting kev ua haujlwm ntawm fibroblasts [21]. Yog li ntawd, kev sib raug zoo thiab kev cuam tshuam mechanism ntawm tooj liab ion overload thiab lub raum fibrosis yog tsim nyog rau kev tshawb nrhiav ntxiv.

Cistanche kho mob raum li cas?

Cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrog kab mob raum. Nws yog muab los ntawm cov stems qhuav ntawm Cistanche deserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Cov khoom tseem ceeb ntawm cistanche yog phenylethanoid glycosides, echinacoside, thiab acteoside, uas tau pom tias muaj txiaj ntsig zoo rau lub raum noj qab haus huv.

Kab mob raum, tseem hu ua kab mob raum, yog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tswv yim.

Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.

Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.

Tsis tas li ntawd, cistanche tau pom tias muaj cov tshuaj tiv thaiv kab mob. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.

Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv cov kab mob hauv lub raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.

Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.

Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.

Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.