Part 1: Cov txiaj ntsig muaj txiaj ntsig ntawm Flavonoids Rau Kev Txhim Kho ntawm Atherosclerosis Los Ntawm Lawv Cov nyhuv ntawm Vascular Smooth Muscle Excitability

Yog xav paub ntxiv, hu rautina.xiang@wecistanche.com

Abstract: Flavonoids yog ib pawg ntawm cov metabolites theem nrab muab tau los ntawm cov khoom noj cog qoob loo, thiab lawv muab ntau yam txiaj ntsig kev noj qab haus huv hauv ntau theem ntawm ntau yam kab mob. Qhov kev tshuaj xyuas no yuav tsom mus rau lawv cov teebmeem ntawm ion channel qhia hauv vascular du leeg thaum lub sijhawm atherosclerosis. Txij li thaum ion channels tuaj yeem tswj hwm los ntawm redox peev xwm, nws xav tias thaum pib ntawm oxidative kev ntxhov siab txog kab mob, ion channels tam sim no hloov pauv hauv lawv cov kev ua haujlwm, cuam tshuam rau kev loj hlob ntawm tus kab mob. Ib qho xwm txheej oxidative kev ntxhov siab ntsig txog yog atherosclerosis, uas cuam tshuam nrog kev ua haujlwm tsis zoo.hlab ntshacov nqaij du. Peb lub hom phiaj los nthuav qhia lub xeev ntawm kev kos duab txog yuav ua li cas redox muaj peev xwm cuam tshuam rau vascular du nqaij ion channel ua haujlwm thiab sau cov ntsiab lus yog tias cov txiaj ntsig tau pom hauv tus kab mob no los ntawm kev siv flavonoids cuam tshuam nrog kev ua haujlwm ntawm ion channel.

Ntsiab lusflavonoids; kev vam meej; atherosclerosis; ion channels; hlab ntsha; cov nqaij du; calcium tam sim no; oxidative kev nyuaj siab; daim nyias nyias; kev txaus siab

1. Taw qhia

Atherosclerosis yog lub hauv paus tseem ceeb ua raukab mob plawv[1,2]; Cov kab mob no tau suav tias yog thawj qhov ua rau tuag thoob ntiaj teb, tshwj xeeb tshaj yog nyob rau hauv cov teb chaws tsim kho thiab cov nyiaj tau los siab, coj lub neej ntawm yuav luag 18 lab tus tib neeg txhua xyoo [3]. Atherosclerosis yog ib yam kab mob uas tshwm sim ntau xyoo thiab tuaj yeem cuam tshuam rau txhua tus neeg, tsis muaj kev txwv tsis pub muaj poj niam txiv neej; Txawm li cas los xij, caj ces thiab ib puag ncig yam xwm txheej ua rau cov neeg tshwj xeeb muaj kev pheej hmoo [4]. Cov teeb meem ntawm tus kab mob no kuj sawv cev rau cov nuj nqis siab rau cov neeg mob thiab cov kab ke kho mob. Yog li ntawd, nws tseem ceeb heev uas yuav tsum tau siv zog los tiv thaiv kev kis tus kab mob no [3,5,6]. Cov kev tiv thaiv tseem ceeb suav nrog kev txhim kho kev noj zaub mov zoo. Kev noj zaub mov uas muaj cov roj ntsha polyunsaturated fatty acids thiab antioxidants nrog kev noj fiber ntau thiab cov khoom noj uas tsis muaj cov khoom noj thiab cov roj saturated fatty acids tau cuam tshuam nrog kev txo qis ntawm cov kab mob plawv. Ib qho piv txwv yog kev noj cov tshuaj antioxidants, xws li ascorbic acid, carotenoids, vitamin E, thiab polyphenols. Ntau cov kev tshawb fawb qhia txog cov txiaj ntsig ntawm kev noj txiv hmab txiv ntoo thiab zaub uas muaj antioxidants hu ua flavonoids [7,8].

Flavonoidsyog cov metabolites theem nrab los ntawm cov nroj tsuag thiab cov pab pawg loj tshaj plaws ntawm cov tshuaj polyphenolic. Muaj ntau tshaj 5000 flavonoids sib txawv nrog ntau yam kev ua ub no. Polyphenols tau kawm ntau heev, txij li thaum Albert Szent-Gyorgyi nrhiav tau lawv nyob rau hauv 1930 thaum nws cais citrine los ntawm txiv qaub thiab hu ua vitamin P. Lub npe no raug xaiv vim hais tias cov molecule tswj cov permeability ntawm capillaries [9]. Peb noj flavonoids hauv peb cov zaub mov tsis tu ncua thaum peb noj txiv hmab txiv ntoo thiab zaub txhua hnub |10]. Lawv muab faib ua pawg: chalcones, aurones, flavones, flavanols, anthocyanidins, flavonols, flavanones, thiab isoflavones [11]. Lawv muaj cov yam ntxwv zoo sib xws uas muab cov khoom noj muaj txiaj ntsig zoo, txawm hais tias lawv muaj qhov sib txawv ntawm kev nqus, metabolism, thiab bioavailability [12]; lawv txhua tus muaj txiaj ntsig zoo rau tib neeg kev noj qab haus huv yog tias noj tsis tu ncua. Cov kev pab hauv vascular noj qab haus huv tshwm sim los ntawm lawv cov kev ua ub no lom neeg ua antioxidants txij li kev tawm tsam rauoxidative kev nyuaj siabtxo qhov kev pheej hmoo ntawm atherosclerosis kev loj hlob [13]. Qee qhov kev ua haujlwm no tau muab los ntawm lawv cov kev cuam tshuam nrog cov pa oxygen reactive (ROS) thiab hom reactive nitrogen (RNS); Txawm li cas los xij, cov teebmeem ntawm ion channel hauv plasmatic membrane ntawm endothelial thiab vascular du leeg hlwb kuj tau tshaj tawm [13,14].

Ion channels yog ib qho tseem ceeb proteins nyob rau hauv plasmatic thiab puab daim nyias nyias. Lawv yog lub luag haujlwm rau kev txav ion hla cov membranes hu ua ion currents. Cov dej ntws no tsim cov kev hloov hauv hluav taws xob ntawm cov hlwb xws li endothelial thiab vascular du leeg hlwb (VSMCs) hauv cov hlab ntsha. Ntau qhov kev tsis txaus ntseeg no cuam tshuam rau cov calcium hauv cov cell hauv lub cev, cuam tshuam cov hlab ntsha 'kev sib cog lus-txo kev cai [14]. VSMCs tsim cov hlab ntsha ntawm phab ntsa thiab tswj txoj kab uas hla ntawm cov hlab ntsha nruab nrab thiab loj. Cov pab pawg neeg no cog lus lossis so kom txaus kom ntshav siab thiab oxygenation ntawm cov ntaub so ntswg. Thaum cov hlab ntsha pib oxidized cholesterol, atherosclerosis tsim, ua rau mob plawv thiab cov kab mob peripheral vascular sib txawv nrog cov neeg mob siab thiab cov neeg tuag [11,15].

Daim ntawv no tham txog kev cuam tshuam ntawm vascular du nqaij ion tam sim no nyob rau hauv kev loj hlob ntawm atherosclerosis thiab yuav ua li cas hloov qhov xwm txheej no tuaj yeem thim rov qab siv flavonoids.

2. Atherosclerosis

Atherosclerosis yog ib yam kab mob tiv thaiv kab mob-metabolic vim nws koom nrog cov hlwb ntawm lub cev tiv thaiv kab mob thiab cov organic molecules ntawm cov metabolism. Atherosclerotic lesions qhia ntau cov monocytes, macrophages, lipoproteins, thiab cov roj cholesterol tsawg. Kev nce qib ntawm tus kab mob yog suav tias yog mob ntev. Nws koom nrog cov txheej txheem degenerative uas tshwm sim hauv ntau theem. Kev puas tsuaj yog tsim nyob rau hauv cov phab ntsa ntawm cov hlab ntsha vim yog txuam nrog lipids, calcium, platelets, thiab lwm yam ntshav compounds [16]. Cov txheej txheem ntawm txoj kev loj hlob ntawm cov quav hniav tshwm sim nyob rau hauv coronary, aorta, carotid, iliac, thiab femoral hlab ntsha tau ntau xyoo [17]. Cov txheej txheem pib nrog kev loj hlob ntawm fatty streak thaum yau; Tom qab ntawd, ib qho fibroatheroma thaum ntxov yog tsim thaum lub hnub nyoog hluas thiab nees nkaum xyoo. Advanced atheroma lossis nyias cap ntawm fibroatheroma tshwm sim hauv cov laus dua 55 xyoo [18].

2.1. Cov Ntsiab Lus

Lub pathogenesis ntawm atherosclerosis tuaj yeem rov pib dua hauv plaub qhov kev xav: (a) oxidative hloov pauv ntawm cov lipoproteins tsawg ntom ntom (LDL) [19,20], (b) teb rau kev puas tsuaj [21], (c) teb rau LDL tuav [22, thiab (d) autoimmune xwm ntawm tus kab mob [23,24](Daim duab 1).Ob qhov kev sim txhawb oxidative LDL hloov kev xav: thawj zaug nws tau pom tias oxidized-LDL (ox-LDL) ua rau kev puas tsuaj rau cov kab mob endothelial [25, 26; Qhov thib ob, ox-LDL tau lees paub los ntawm cov khoom siv scavenger sib txawv (Lectin-zoo li oxidized LDL receptor-1(LOX-1) suav nrog scavenger receptors uas khi LDL (CD36), scavenger receptors rau phosphatidylserine thiab oxidized LDL hauv tib neeg. Cov kab mob atherosclerotic (SR-PSOX), thiab multifunctional receptors hauv atherosclerosis (SR-A macrophage receptors), uas kho cov lipids nkag mus rau hauv macrophages.

Qhov thib ob hypothesis txiav txim siab tias qhov kev puas tsuaj tshwm sim rau lubhlab ntshaendothelium yog lub luag haujlwm rau kev ua haujlwm ntawm endothelial thiab pib ntawm cov txheej txheem atherosclerotic. Cov txheej txheem suav nrog kev nce permeability ntawm lipoproteins thiab kev qhia ntawm adhesion molecules, xws li E-selectin, P-selectin, vascular endothelial cell adhesion molecule-1(VCAM-1), thiab intercellular adhesion molecule{{ 4}} (ICAM-1). Cov molecules khi rau lawv cov receptors sib xws ntawm cov kab mob monocytes thiab T lymphocytes thiab ua rau cov neeg ua haujlwm ntawm cov hlwb no mus rau qhov chaw raug mob, qhov twg ROS hom los ntawm fibroblast thiab lwm cov hlwb ua rau atherogenesis [28].

Qhov thib peb hypothesis suav tias yog kev tuav cia ntawm LDL ua ntej. Kev sib sau ntawm lipoproteins nyob rau hauv cov phab ntsa hlab ntsha thiab arterial proteoglycans tuaj yeem ua rau cov kab mob pro-inflammatory thiab txhawb atherosclerosis [29,30]. Qhov thib plaub hypothesis muaj feem xyuam rau qhov tsis yooj yim ntawm autoimmune xwm; Qhov no suav nrog kev tiv thaiv kab mob ua ntej kev txhim kho cov quav hniav. Thaum pib ntawm tus kab mob, antigens, antibody complexes, T lymphocytes, B lymphocytes, thiab cov proteins ntawm lub complement system koom, thiab infiltration ntawm mononuclear hlwb rau hauv qhov txhab, xws li CD8 ntxiv lymphocytes, CD4 * (Th1) pab T lymphocytes, mast hlwb, monocytes, thiab macrophages, tshwm sim. DAMPs (kev puas tsuaj-txuas nrog cov qauv molecule) xws li cov proteins thaum kub ntxhov (HSP) thiab ox-LDL tshwm; Qhov tseeb, cov tshuaj tiv thaiv HSP60 tuaj yeem siv los ua tus cim kab mob rau kev loj hlob. Innate immune cells paub txog ox-LDL thiab HSPs thiab qhibmob; tag nrho cov xwm txheej no txhawb nqa qhov tseem ceeb ntawm kev tiv thaiv kab mob thaum txhim kho kab mob [31-33].

Ib qho ntawm plaub txheej txheem no ua rau atherosclerosis, tab sis nws tuaj yeem tiv thaiv tau los ntawm kev txo qis ntawm kev pheej hmoo. Cov yam ntxwv tseem ceeb ntawm atherogenic yog kev rog rog, oxidative stress, dyslipidemia, hyperglycemia, thiab pro-inflammatory xeev 34,35]. Cov kev tshawb fawb tau tshaj tawm tias cov ntshav siab ntau ntawm LDL-cholesterol, qabzib thiab C-reactive protein (CRP) ncaj qha cuam tshuam nrog kev pheej hmoo ntawm kev mob plawv [35,36].

Nws yog ib qho tsim nyog yuav tsum nkag siab txog cov ntsiab lus ntawm tus kab mob pathophysiology los tsim cov kev tiv thaiv tsim nyog thiab / lossis cov tswv yim kho mob uas tuaj yeem zam cov vascular calcification [37J. Thaum lub sij hawm tus txheej txheem no, lub predominant cell hom nyob rau hauv lub arterial phab ntsa yog du leeg hlwb; lawv yog lub luag haujlwm rau cov qauv ntawm cov hlab ntsha thiab kev ua haujlwm ncaj ncees [21]. Calcification yog tsim nyob rau hauv intima ntawm cov hlab ntsha ntawm cov ntsiab lus tshwj xeeb uas tsim siv lead ua thaj ua rau thaj nrog necrotic core chaw [37,38]. Thaum pib ntawm atherosclerotic theem, cov leeg nqaij du yog 90 feem pua ​​​​ntawm cov ntsiab lus cellular nyob rau hauv qhov chaw mob. Txawm li cas los xij, qhov no hloov pauv hauv cov kab mob siab heev; Nyob rau hauv cov ntaub ntawv no, lub extracellular matrix predominates tshaj cov leeg nqaij hlwb, tsim cov fibrous npog ntawm plaques. Cov leeg nqaij du nrog cov kab mob uas tsis yog-proliferative contractile phenotype yog hloov mus rau hauv cov hlwb uas nquag proliferate, migrate attracted los ntawm chemotactic agents, thiab tsim extracellular matrix proteins (collagen, elastin, thiab proteoglycans). Qhov kev hloov pauv no ua rau muaj kev qhia ntawm cov noob uas encode mem-brane receptors rau kev loj hlob yam [22]. Kev tsiv teb tsaws ntawm cov leeg nqaij pob txha txhawb nqa calcification nyob rau hauv qhov chaw raug mob, uas yog txuam nrog kev tuag ntau dua thiab morbidity [39].

Lub spontaneous rupture ntawm ib tug atherosclerotic plaque ua rau lub activation ntawm pro-thrombotic ntsiab ntawm endothelium. Thaum platelets sib sau ua ke, lawv tso tawm lawv cov granules nplua nuj nyob rau hauv mitogens thiab induce lub migration thiab proliferation ntawm cov leeg nqaij hlwb, nrog rau o thiab oxidative kev nyuaj siab, uas muaj nyob rau hauv tag nrho cov theem ntawm tus kab mob [40,41].

2.2. Cov theem ntawm Atherosclerosis

Muaj ib txoj hauv kev los txheeb xyuas qhov kev loj hlob ntawm atherosclerosis raws li kev tshawb fawb histological los ntawm tib neeg thiab tsiaj autopsies nyob rau theem hauv qab no: ua ntej atherosclerosis, ntxov atherosclerosis, lig atherosclerosis, thiab kev kho mob sequelae [42,43]. Nyob rau hauv txhua theem, vascular du leeg hlwb yog qhov tseem ceeb rau kev loj hlob ntawm cov quav hniav. Pre-atherosclerosis pib thaum yug los vim qhov sib txawv ntawm qhov sib txawv ntawm qhov sib txawv thiab cov xanthomas intimal yog siv los ua kev hloov pauv rau cov ntshav ntws[44-46]; Qhov no suav hais tias yog pre-plaque [42]. Thaum ntxov atherosclerosis, pathological intima thickening yog tsim. Cov plaque thaum ntxov no muaj cov lipid sab hauv lub pas dej sib sib zog nqus hauv qhov intima nrog ntau ntau ntawm VSMCs thiab extra-cellular matrix (ECM) [42,43]. Kev nce qib suav nrog kev tuav thiab oxidation ntawm LDL, induction ntawm o, thiab VSMCs proliferation, nrog phenotypic hloov thiab tuag [22,47]. VSMCs tsim ECM nyob rau hauv lub intima, uas nws plays lub luag hauj lwm tseem ceeb nyob rau hauv pib ntawm atherosclerosis. Thaum lub sij hawm tus txheej txheem no, nws tau pom tias tsis zoo them nyiaj sab chains ntawm proteoglycans cuam tshuam nrog rau qhov zoo them sab ntawm apolipoproteins [48] kom khaws lipoproteins ntawm plasma [30]. Cov lipoproteins daig raug oxidation, macrophages raug recruited, thiab o pib [22]. Qee zaum, micro-calcification nyob ze ntawm cov ntaub so ntswg tshwm sim, uas tau cuam tshuam nrog VSMC apoptosis [49]. Pathological intima thickening nyob rau theem lig ib txwm nthuav tawm nrog ntau cov macrophages, sawv cev rau cov kauj ruam tseem ceeb rau kev loj hlob mus rau fibroatheroma [50-54] thiab VSMCs 'proliferation, migration, thiab phenotype hloov [55]. Thaum lub sij hawm lig, lub tsub zuj zuj ntawm macrophages nyob rau hauv lub luminal qhov chaw yog tsim nyog. Cov kab mob yog tus cwj pwm los ntawm lub hau fibrous thiab necrotic core, uas yog tsim los ntawm VSMCs tuag thiab macrophages uas phagocyte lipids thiab ua npuas hlwb [56,57]; Tom qab ntawd, fibroatheroma tsim, thiab calcification tuaj yeem pom thawj zaug hauv cov tub ntxhais necrotic thiab tom qab ntawd nyob rau hauv ib puag ncig ECM [58-60]. Cov quav hniav no paub tab tsim cov ntawv uas nws cov khoom tawg tuaj yeem nkag mus rau hauv lub lumen thiab ua rau cov thrombosis [42,60]. Thaum kawg, kev kho mob sequelae nyob ntawm seb cov hlab ntsha twg tau raug cuam tshuam [6].

2.3. Lub luag haujlwm ntawm Oxidation

ROS thiab RNS hom yog tsim nyob rau hauv tsawg concentrations nyob rau hauv VSMCs, adventitia, thiab endothelial hlwb nyob rau hauv ib txwm tej yam kev mob. Lawv ua haujlwm ua tus neeg nruab nrab hauv xov tooj ntawm tes los tswj kev ua haujlwm ntawm cov hlab ntsha[13,62-64], koom nrog cov leeg nqaij pob txha loj hlob, thiab tswj kev cog lus thiab so [65,66]. Txawm li cas los xij, thaum lub xeev pathological, muaj qhov tsis sib xws ntawm cov tshuaj tiv thaiv antioxidants thiab oxidants, thiab thaum oxidants tau txais txiaj ntsig, oxidative kev nyuaj siab yog tsim. Cov peev txheej ntawm ROS suav nrog lipooxygenases, cytochrome P450, cyclooxygenase, xanthine oxidase, mitochondrial respiration, NADPH oxidase, thiab uncoupled nitric oxide synthases[13]. Tsis tas li ntawd, intracellular ROS ntau lawm tuaj yeem muab tau los ntawm cov saw hluav taws xob thauj mus los [67]. Ib qho ntawm thawj cov ntaub so ntswg cuam tshuam hauv atherosclerosis yog endothelium, qhov twg nitric oxide (NO), endothelin I, angiotensin II, adhesion molecules, thiab cytokines raug tsim [13,68]. Oxidative kev nyuaj siab cuam tshuam rau cell functions, tsim endothelial dysfunction, thiab txo NO synthesis; txo bioavailability ntawm NOexerts atherogenic teebmeem [69]. Ib qho tseem ceeb uas tsis tau tshawb pom tob yog yuav ua li cas oxidative stress modulates ion channel oxidation hauv VSMCs thaum lub sij hawm kev loj hlob ntawm atherosclerosis. Ion channels sawv cev rau cov ntsiab lus transcendental rau kev ua haujlwm zoo ntawm VSMCs; Yog tias lawv txoj haujlwm raug cuam tshuam, nws yog ib qho tseem ceeb kom paub meej tias qhov no cuam tshuam li cas rau kev txhim kho kab mob [70].

ROS thiab RNS tuaj yeem cuam tshuam rau ion channel ncaj qha lossis tsis ncaj qha: ncaj qha los ntawm kev tsim cov kev hloov pauv tom qab kev hloov pauv ntawm cov proteins, xws li nitrosylation, sulfhydration, lossis nitration ntawm cov amino acid residues; los sis tsis ncaj los ntawm kev hloov cov teeb liab sib txawv. Sulfur atoms nyob rau hauv cysteine ​​​​thiab methionine qhia qhov rhiab heev rau redox muaj peev xwm nrog rau cov nplhaib uas muaj ntxhiab los ntawm histidine, phenylalanine, tryptophan, thiab hydroxyl pawg hauv tyrosine residues [14]. Lub siab reactivity ntawm thiol pab pawg neeg ntawm cysteine ​​​​muaj txhawb rau kev tsim ntawm sulfenic acid, sulfinic acid, los yog sulfonic acid, nyob ntawm seb oxidant concentration thiab cov tshuaj tiv thaiv tej yam kev mob; methionine tsim methionine sulfoxide thiab methionine sulfone; histidine oxidizes rau 2-hexahistidine, thiab tryptophan oxidizes rau 5-hydroxytryptophan thiab oxindolealanine [71]. Cysteine ​​tuaj yeem raug kev txom nyem lwm yam kev hloov pauv xws li nitrosylation thiab glutathionylation [70]. Piv txwv li, nyob rau hauv vascular du leeg hlwb, ROS thiab TSIS muaj peev xwm oxidize voltage-gated calcium channels Cav1.2b cysteine ​​residues nyob rau hauv lub alpha subunit thiab tsim conformational hloov [14].

2.4. Kev puas tsuaj hauv Vascular Smooth Muscle Cells

Vascular du leeg hlwb nthuav tawm qhov sib txawv ntawm qhov qhia txog cov proteins, receptors, thiab ion channels piv rau cov leeg nqaij thiab pob txha. Nws qhov kev cog lus yog qhov sib txawv vim tias VSMCs tsis muaj peev xwm ua tau. Lawv tau cog lus ib nrab ntawm so, ua rau lawv cov contractility nyob rau hauv teb rau neuronal, humoral, los yog endothelial stimulus ua rau daim nyias nyias receptors. Qhov kev cog lus no kuj qeeb thiab qee zaum tuaj yeem txhawb nqa thiab tonic [72]. Kev saib xyuas ntawm vascular tone yog tswj los ntawm VSMC membrane peev xwm. Depolarization activates L-hom high voltage-gated calcium channels (Cav1.2) ntawm plasma membrane, pib nce Ca2 ntxiv rau kev nkag [73]

Qhov nce hauv intracellular Ca2 txhawb kev cog lus teb los ntawm kev ua kom cov calcium calmodulin-dependent myosin light chain kinase (MLCK) thiab tso ntau Ca2 ntxiv los ntawm cov khw muag khoom calcium hauv intracellular [74]. Ntawm qhov tod tes, K ntxiv efflux los ntawm Ca2 ntxiv -activated K channels (KCa) modulates daim nyias nyias muaj peev xwm tsis ncaj vim lawv txwv qhov ntws ntawm Ca2 ntxiv rau hauv cov hlwb, ua rau Cav1.2 inhibition [75]. Lub vascular du leeg cell membrane muaj ntau hom kab. Ntawm cov calcium channels, peb muaj raws li lub ntsiab regulators L-hom raws, xws li Cav1.2b, uas yog ib tug txawv isoform los ntawm Cav1.2a nyob rau hauv lub plawv nqaij [14]. Lawv yog cov tseem ceeb regulators ntawm vascular du nqaij [Ca2] I thiab contractility. Cov channel no ua haujlwm ntawm ob theem sib txawv: depolarization thiab hyperpolarization. Cov pab pawg tswj hwm ntawm depolarization suav nrog cov tsev neeg muaj peev xwm hloov pauv hloov pauv (TRP), TRPC3, TRPC6, thiab TRPM4 raws, thiab pab pawg txhawb nqa hyperpolarization suav nrog kev ua haujlwm tseem ceeb calcium-activated potassium channels, TRPV4, thiab Cav3.2 raws. Kev nkag ntawm calcium rau hauv lub cell feem ntau yog kho los ntawm L-hom channels (Cav1.2b) thiab, rau qee qhov, T-hom Cav3.1/3.3 channels; lawv tswj kev cog lus, thiab lawv txoj haujlwm yog tswj hwm los ntawm kev hloov pauv hauv daim nyias nyias [76].

Lwm cov channel hauv plasma membrane muaj xws li chloride channels. Lawv muaj ntau lub luag haujlwm, suav nrog kev tswj hwm ntawm tes, kev thauj mus los ntawm transepithelial, ion homeostasis, thiab kev tswj hwm ntawm hluav taws xob excitability [77]. Hauv cov leeg nqaij du, lub peev xwm electrochemical rau chloride yog siab dua qhov muaj peev xwm so. Tom qab ntawd, qhib cov chloride channel yuav tsim kom txaus depolarization los ua kom muaj zog ntawm Cav channels thiab Ca2 ntxiv rau influx, uas yog ib qho tseem ceeb rau vascular teb rau mechanical stress [78].

Membrane ion channels ntawm VSM raug cais raws li hauv qab no:

(a) Voltage-gated Ca channels (VGCC).Cov channel no tswj kev cog lus thiab cov noob qhia hauv VSCM. L-type thiab T-type Ca channels yog cov neeg sawv cev ntawm tsev neeg no. Thaum L-hom channel tau qhib, daim nyias nyias yog depolarized, thiab calcium ions nkag mus rau hauv cytoplasm; Tom qab ntawd, cov poov tshuaj raws tau qhib, thiab daim nyias nyias hyperpolarization tshwm sim nrog rau tom qab deactivation ntawm VGCCs [79]. Kev ua kom PKG pab txhawb rau vasodilation mediated los ntawm NO thiab inhibits Cav1.2 tam sim no [80].

T-hom channels tuaj yeem ua rau cov suab nrov myogenic ntawm qhov tsis tshua muaj siab intravascular thaum cov leeg nqaij pob txha yog cov hyperpolarized; Txawm li cas los xij, lawv lub luag haujlwm tshwj xeeb yuav tsum tau piav qhia ntxiv [81].

(b)Ca2- qhib K channels (KCa).Cov channel no tau qhib nrog kev nce Ca2 ntxiv rau hauv lub cev concentration; BKCas muaj ntau tshaj plaws hauv VSMCs. Txog rau tam sim no, tsuas yog ob txoj kev tshawb fawb tau txheeb xyuas cov kab hluav taws xob me me calcium-activated potassium channels (SK Ca) hauv VSMCs los ntawm cov hlab ntsha hauv lub cev [82], thiab nruab nrab conductance calcium-activated potassium channels (IKCa) tsuas yog qhia hauv proliferating VSMCs [83] .

(c) Voltage-gated K plus channels (Kv).Lawv pab txhawb rau lub suab so ntawm cov hlab ntsha me me thiab yog lub zog dilator hauv cov hlab ntsha. Kv1.X yog cov pab pawg tseem ceeb ntawm voltage-gated potassium raws hauv VSMC ntawm coronary microvessels. Cov neeg hauv tsev neeg hauv cov hlab ntsha muaj xws li Kv1.2 thiab Kv1.5. Kev tsim tawm siab ntawm peroxynitrite hauv hyperglycemia cuam tshuam rau cov Kv channel thiab cuam tshuam cov leeg nqaij leeg [84]. Lawv tswj cov hlab ntsws thiab tswj cov vascular remodeling hauv pulmonary artery du leeg hlwb [71].

(d) Transient receptor muaj peev xwm channel (TRP).Raws li homology ib ntus, hom channel no tau muab faib ua rau rau tus tswv cuab: canonical(TRPC1-7), melanostatin (TRPM1-8), vanilloid (TRPV1-6), ankyrin(TRPA1), polycystin (TRPP1-3), thiab mucolipin (TRPML1-3). Txhua tsev neeg muaj qhov sib txawv ntawm cov khoom thiab cov qauv [85].

Table 1 qhia txog cov neeg sawv cev tshaj plaws nyob rau hauv VSMC, lawv cuam tshuam li cas los ntawm oxidative kev nyuaj siab, qhov tshwm sim hauv daim nyias nyias, thiab lawv koom nrog atherosclerosis li cas.

Tsis tas li ntawd, cov nqaij mos excitability yog modulated indirect los ntawm cytoplasmic calcium concentration tso tawm los ntawm mitochondria thiab sarcoplasmic reticulum [86].

2.5. Natural Compounds rau Kev Kho Mob Atherosclerosis

Ntau cov nroj tsuag derivatives yog siv los ua tshuaj; lawv cov txiaj ntsig muaj xws li cov teebmeem thib ob tsawg thiab txo cov kev ntxhov siab oxidative, LDL cholesterol, thiab o [87]. Kev siv cov khoom siv ntuj tsim hauv atherosclerosis tau tsom mus rau kev tiv thaiv lossis kev kho mob kom txo qis cov ntshav lipids. Ntawm cov khoom siv sib txawv, nws tau pom tias kev noj cov tshuaj polyphenol xws li flavonoids pab txo qis kev txhim kho atherosclerosis vim tias nws muaj zog tiv thaiv kab mob antioxidant [88], Kev noj zaub mov Mediterranean, uas suav nrog kev noj cov roj txiv roj thiab txiv ntoo, txo cov hlab plawv. Kab mob tshwm sim los ntawm 30 feem pua ​​​​piv rau cov khoom noj muaj roj tsawg uas cuam tshuam nrog nws cov ntsiab lus phenolic siab [89]. Qhov txo qis ntawm thaj chaw atherosclerotic lesion tau pom nrog kev kho mob flavonoid nyob rau hauv kev tshawb fawb sib txawv ntawm ex yivyo nyob rau hauv aortas ntawm hloov Apo E nas [o0-o4] Cov ntsiab lus ntawm ntau yam txiaj ntsig ntawm flavonoids hauv cov kab mob plawv yog qhia hauv Table 2.

Nyem qhov txuas kom tau txais cov ntaub ntawv ntxiv
https://www.xjcistanche.com/news/part2-potential-benefits-of-flavonoids-on-the-55147397.html