Attenuation Of Experimental Autoimmune Uveitis in Lewis nas Los ntawm Betaine

Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv

Kev sim autoimmune uveitis (EAU) yog tus qauv tsiaj ntawm tib neeg autoimmune uveitis uas yog tus cwj pwm los ntawm kev nkag mus ntawm autoimmune T hlwb nrog kev nce ntxiv hauv cov cytokines pro-inflammatory thiab reactive oxygen hom. Txoj kev tshawb no tsom los ntsuas seb betaine tswj kev nce qib ntawm EAU hauv Lewis nas. EAU raug ntxias los ntawm kev txhaj tshuaj nrog interphotoreceptor retinoid-binding protein (IRBP) thiab kev tswj qhov ncauj ntawm lub tsheb lossis betaine (100 mg / kg) rau 9 hnub sib law liag. Spleens, ntshav, thiab retinas raug kuaj los ntawm cov nas sim thaum lub sijhawm txi thiab siv rau T cell proliferation assay, serological tsom xam, real-time polymerase saw cov tshuaj tiv thaiv, thiab immunohistochemistry. Qhov kev ntsuam xyuas T cell proliferation tau qhia tias betaine muaj kev cuam tshuam me ntsis rau kev loj hlob ntawm splenic T cells tiv thaiv IRBP antigen hauv kev tshuaj ntsuam hauv vitro rau hnub 9 tom qab txhaj tshuaj. Kev soj ntsuam serological pom tau hais tias qib ntawm cov piam thaj superoxide dismutase nce hauv pawg betaine-kho piv nrog rau hauv pab pawg kho tsheb.cistanche tubulosa extractCov tshuaj tiv thaiv kab mob ntawm betaine tau lees paub los ntawm kev txo qis ntawm cov tshuaj tiv thaiv kab mob ntsig txog kab mob, suav nrog vascular cell adhesion molecule I thiab interleukin -1 hauv cov retinas ntawm nas nrog EAU. Cov kev tshawb pom histopathological tau pom zoo nrog cov ionized calcium-binding adapter molecule l immunohistochemistry, ntxiv kev tshawb xyuas ntxiv tias qhov mob hauv lub retina thiab ciliary lub cev tau cuam tshuam loj heev hauv pab pawg kho betaine piv nrog cov pab pawg kho tsheb. Cov txiaj ntsig ntawm kev tshawb fawb tam sim no qhia tias betaine koom nrog hauv kev txo qis EAU los ntawm kev tiv thaiv oxidation thiab tiv thaiv kev ua haujlwm.

Thov nias ntawm no kom paub ntxiv

Lo lus tseem ceeb:Anti-o, Anti-oxidation, Betaine, Kev sim autoimmune uveitis, Retina

Taw qhia

Lub homing ntawm autoreactive T hlwb thiab infiltration ntawm inflammatory hlwb, xws li monocytes, ua rau uveitis thiab retinitis nyob rau hauv EAU [6]. Lub retina puas lawm los ntawm o nrog kev ua kom cov hlwb glial uas dhau oxidative kev nyuaj siab [7].

Betaine, tseem hu ua trimethylglycine (CH: TSIS TAU:), yog ib qho alkaloid thiab nontoxic natural tshuaj los ntawm Fructus Lycia, thiab ib tug sawv cev antioxidant tshuaj [8]. Betaine txhim kho cov hnub nyoog ntsig txog kev mob hauv cov nas los ntawm kev koom tes ntawm nuclear-kB kev cuam tshuam los ntawm kev cuam tshuam ntawm nuclear-inducing kinase/I kappa B kinase thiab mitogen-activated protein kinases [9], tib neeg cov kab mob plawv los ntawm suppressing inflammatory cytokines, suav nrog interleukin (IL) {{ 6}} thiab qog necrosis factor-a(TNF-a)[10], thiab dextran sulfate sodium-induced colon tumorigenesis [11].cistanche tubulosa tshuaj xyuas,Tsis tas li ntawd, betaine tiv thaiv pathological angiogenesis / neovascularization nyob rau hauv cov nas uas muaj ntshav qab zib retinitis [12] thiab tiv thaiv cov kab mob hauv lub hlwb kom ua rau pom kev pom ntawm tus tsiaj qauv ntawm glaucoma [13]. Txawm li cas los xij, tsis muaj kev paub me ntsis txog cov txheej txheem meej hauv qab cov teebmeem ntawm betaine hauv uveitis.

Hauv txoj kev tshawb no, qhov ua tau zoo ntawm betaine hauv kev txo qis EAU tau raug soj ntsuam. Peb tshawb xyuas cov tshuaj tiv thaiv kab mob ntawm betaine hauv EAU raws li kev soj ntsuam histopathological thiab ntsuas cytokine. Tsis tas li ntawd, cov txheej txheem tshwj xeeb ntawm betaine ua cov tshuaj tiv thaiv antioxidant tau soj ntsuam hauv nas nrog EAU.

KHOOM PLIG THIAB MUAB

Tsiaj txhu

Ob leeg poj niam ntawm Lewis nas (7 ~ 9 lub lis piam; Orient Bio Inc, Gyeonggi-do, Kauslim Teb) tau nyob hauv peb qhov chaw nyob rau hauv qhov chaw kuaj mob (12-h lub teeb / tsaus voj voog, kub 23 ± 2 degree ). Tag nrho cov txheej txheem kev sim tau ua raws li Cov Lus Qhia rau Kev Saib Xyuas thiab Kev Siv Cov Tsiaj Txhaum Cai ntawm Jeju National University (tus naj npawb tso cai:2020-0012). Tag nrho cov kev cai tsiaj ua raws li txoj cai thoob ntiaj teb thiab NIH cov cai, suav nrog Kev Saib Xyuas thiab Siv Cov Tsiaj Txhaum Cai (NIH ntawv tshaj tawm no.85-23,1985, hloov kho 1996).

Induction ntawm EAU

Cov nas tau txhaj tshuaj nrog 200 ul ntawm ib qho emulsion sib xyaw ua ke ntawm qhov sib npaug ntawm bovine interphotoreceptor retinoid-binding protein (IRBP) (I mg / ml; PTARSVGAADGSS-WEGVGVVPDV, Komabiotech, Seoul, Republic of Kauslim) thiab Freund's tiav adjuvant (C. ) ntxiv nrog rau kuv mg/mL Mycobacterium tuberculosis H37Ra (Difco Laboratories Inc., Detroit, MI, USA) rau ntawm cov pob txha ntawm lawv cov ceg pob txha.

Cov pab pawg sim

Txhawm rau ntsuas qhov cuam tshuam ntawm betaine (Fig.1A) ntawm EAU, plaub pawg sim tau raug xaiv raws li hauv qab no: kev tswj ib txwm (n=8); CFA tswj (n=8); EAU plus Tsheb (n=8); thiab EAU plus Betaine(n=8). 0 mg/kg lub cev hnyav/hnub, B2629, Sigma-Aldrich, St.Louis, MO, USA) raug xaiv raws li kev kawm yav dhau los [14]. Cov nas tsuag tau kho qhov ncauj 9 nrog betaine txij hnub 0 tom qab txhaj tshuaj mus txog hnub 9 tom qab txhaj tshuaj.

Kev npaj cov ntaub so ntswg

Cov nas tau muab txi rau hauv qhov sib sib zog nqus tshuaj loog ntawm CO2 pa nqus pa rau hnub 9 tom qab txhaj tshuaj.cistanche UKCov ntaub so ntswg rau kev kuaj histopathological tau muab tso rau hauv paraffin siv quav ciab thiab cais

nrog microtome (RM 2135; Leica, Nussloch, Lub teb chaws Yelemees) mus rau ib lub thickness ntawm 5 um thiab stained nrog hematoxylin thiab eosin. Ntshav thiab retinas tau khaws cia ntawm -80 degree rau kev tsom xam cov ntshav thiab cov tshuaj tiv thaiv kab mob ntawm cov tshuaj polymerase (PCR) real-time.

T cell proliferation assay

Spleen mononuclear hlwb los ntawm cov tsiaj nyob rau hauv txhua pab pawg tau dissociated thiab raug tshem tawm raws li tau piav nyob rau hauv peb kev tshawb fawb yav dhau los [15]. Tom qab ntawd, 10 ug / ml IRBP (qhov kawg concentration) tau ntxiv rau hauv qhov dej. Tom qab 48 h ntawm stimulation nrog IRBP, cov hlwb raug incubated nyob rau hauv 1 μCi ntawm 'H-methyl thymidine (kev ua ub no 42 Ci / mmol; Amersham, Arlington Heights, IL, USA) rau 18 teev. Tom qab ntawd, cov hlwb raug sau los ntsuas thymidine incorporation.

Cistanche tuaj yeem tiv thaiv kev laus

Kev soj ntsuam Serological

Cov nas tau muab txi rau hnub coj mus kuaj, thiab cov ntshav tau sau los ntawm lub plawv. Cov ntshav tag nrho tau muab cais ua cov ntshav thiab cov qe ntshav uas siv lub centrifuge (VS-5500CFN; Vision Scientific, Daejeon, Republic of Kauslim). Superoxide dismutase (SOD) kev ua hauv cov ntshav tau soj ntsuam siv cov khoom siv SOD (ab65354; Abcam, Cambridge, UK).

Immunohistochemistry

Immunohistochemistry tau ua tiav siv tib txoj cai raws li tau piav qhia hauv peb txoj kev tshawb fawb dhau los [16].Cov tshuaj tiv thaiv thawj zaug suav nrog ionized calcium-binding adapter moleculel (Ibal)(1: 1, 000;019-19741, Wako Pure Chemical Industries, Ltd, Osaka, Nyiv), CD68 (ED1; 1: 800; MCA341, Serotec, Kidlington, UK), thiab glutamine synthetase (GS) (1: 5, 000; MAB302, Chemicon Hauv -ternational, Temecula, CA, USA) tau siv los ua tus cim rau microg-lia, macrophage thiab Müller cell, feem.

Real-time PCR

Tag Nrho RNA hauv cov pob muag hauv txhua pab pawg (n{0}} ib pawg) raug cais nrog TRIzol RNA Isolation Reagent (Lub Neej Technologies, Thermo Fisher Scientific, Carlsbad, CA, USA), thiab cDNA tau npaj siv CellScript M All-in -Ib 5X First Standard cDNA Synthesis Master Mix (CellSafe, Gyeonggi-do, Republic of Kauslim). Cov ntaub ntawv primer yog teev nyob rau hauv Table 1. PCR tau ua nrog MIC cycler (BMS, Queensland, Australia) siv 2x SYBR Green (PhileKorea, Seoul, Republic of Kauslim) thiab cov kev pab cuam hauv qab no: 55 cycles of denaturation (5 s,95). degree), annealing (20s, 60 degree), thiab txuas ntxiv (10s, 72 degree).

Western blot tsom xam

Western blot tsom xam tau ua los ntawm tib txoj cai raws li tau piav qhia hauv peb txoj kev tshawb fawb dhau los [16].cistanche wrkungCov tshuaj tiv thaiv tseem ceeb suav nrog Kelch-zoo li ECH-koom nrog cov protein 1 (Keap1)(1:1,000;abl19403,abcam,MA,USA), thiab Nuclear factor erythroid-2-re-lated factor2(Nrf2 )(1:1,000; sc-722,Santa cruz,CA,USA).

Kev txheeb cais

Txhua qhov ntsuas tau tshaj tawm raws li qhov nruab nrab ntawm peb qhov kev sim ywj pheej. Tag nrho cov txiaj ntsig tau nthuav tawm raws li tus qauv kev ua yuam kev ntawm qhov nruab nrab (SEM). Cov txiaj ntsig tau raug tshuaj xyuas siv ib txoj kev tsom xam ntawm qhov sib txawv ua raws li Tub Ntxhais Kawm-Newman-Keuls posthoc xeem rau ntau qhov sib piv. Ib p-value<0.05 was="" considered="" to="" indicate="" significance.="" immunostaining="" was="" analyzed="" semi-quantitatively="" based="" on="" the="" positive="" areas="" in="" the="" photographs="" using="" imagej="" software="" (national="" institutes="" of="" health,="" bethesda,="" md,="" usa).eau="" was="" histopathologically="" evaluated="" using="" a="" method="" modified="" from="" a="" previous="" study="" [17].="" antibody-positive="" areas="" were="" measured="" as="" follows:(1)three="" different="" sections="" from="" each="" rat="" (n="3" animals="" per="" group)="" were="" used;="" then,="" (2)="" the="" percentage="" of="" the="" stained="" area="" [(positive="" area/total="" area)x100(%)]="" was="" calculated.="" the="" total="" area="" included="" all="" layers="" of="" the="" retina.="" these="" results="" are="" presented="" as="" the="">

TSEEM CEEB

Betaine had no immunomodulatory function in EAU The T cell proliferation assay was performed to determine whether betaine affected the proliferation of IRBP-specific T cells (Fig.1B). No significant changes were observed between the EAU-induced groups in medium only and those that were IRBP-stim-ulated (medium only, p>0.05 vs.EAU+Vehicle; IRBP stimulation, p>0.05 vs.EAU plus Tsheb). Cov ntaub ntawv no qhia tau hais tias betaine tsis koom nrog IRBP tshwj xeeb T hlwb lossis lawv qhov pib-reactivity.

Betaine upregulated serum SOD qib hauv EAU

Peb soj ntsuam oxidative puas nyob rau hauv cov ntshav, siv SOD ua tus cim ntawm oxidative hloov. Tsis muaj qhov sib txawv tseem ceeb ntawm pawg ib txwm muaj thiab CFA. SOD kev ua haujlwm tau txo qis hauv EAU ntxiv rau pawg tsheb, piv rau qib hauv kev tswj hwm ib txwm muaj thiab CFA pawg. Kev kho mob Betaine tau rov qab kho cov qib ntawm SOD kev ua haujlwm rau qhov kev tswj hwm ib txwm muaj thiab CFA pawg (Fig. 2). Qhov txiaj ntsig no qhia tau tias kev kho betaine txo qis oxidative kev nyuaj siab hauv nas nrog EAU.

Betaine txo qhov infiltration ntawm Ibal-zoo hlwb hauv lub cev ciliary thiab retinas ntawm EAU-vim nas.

Lub cev ciliary yog lub ntsiab inflammatory cell infiltration site vim muaj ntau ntawm cov hlab ntsha [18]. Tsuas yog ob peb lub hlwb puag ncig tau kuaj pom nyob rau hauv lub cev ciliary hauv ib txwm thiab CFA pawg (Fig. 3A,3B), whereas infiltration ntawm qee lub hlwb puag ncig tau lees paub hauv pawg EAU-induced (cov xub hauv Fig.3C , 3D ib). Cov pab pawg ib txwm muaj (Fig.3E) thiab CFA (Fig.3F) tsis tu ncua pom cov txiaj ntsig zoo sib xws rau cov neeg pom zoo rau Ibal immunoreactivity. Ibal-zoo immunoreactivity tau nce hauv EAU ntxiv rau Tsheb thiab EAU ntxiv rau Betaine pawg (cov xub xub hauv Fig.3G, 3H). Txawm li cas los xij, tus lej ntawm Ibal-zoo hlwb tau txo qis qhov tseem ceeb hauv pawg EAU ntxiv rau Betaine piv rau pawg EAU ntxiv rau Tsheb (Daim duab 3I). Peb kuj tau txheeb xyuas qhov chaw ntawm EDI raws li ib txoj hauv kev ntxiv los ntsuas qhov tseeb qhov chaw ntawm cov kab mob inflammatory cell infiltration hauv lub cev ciliary.ED1-cov hlwb tsis tshua pom muaj nyob hauv qhov qub (Fig. 3G) thiab CFA (Fig. 3K ) pab pawg. Los ntawm qhov sib txawv, ntau ED1-cov hlwb zoo tau kuaj pom hauv EAU ntxiv rau Tsheb thiab EAU ntxiv rau Betaine pawg (ob npaug xub xub hauv Fig.3L,3M).Citrus bioflavonoidsIb qho kev ntsuam xyuas ib nrab ntawm cov naj npawb ntawm ED1-cov hlwb zoo tau lees paub tias kev kho betaine inhibited infiltration ntawm inflammatory cells nyob rau hauv ciliary lub cev ntawm EAU-induced nas.

Tom ntej no, peb tshawb xyuas cov kev hloov pauv histopathological hauv retina (Fig. 4). Ob peb lub hlwb inflammatory tau kuaj pom nyob rau hauv retinas nrog EAU, tab sis tsis nyob rau hauv ib txwm thiab CFA nas retinas (Fig.4A ~ 4D). Cov kab mob tau qhab nia histopathologically raws li qhov hnyav ntawm EAU [17], nthuav tawm kev kho mob ntawm qhov muag pom (Fig.4E). Microglial thiab Müller cell activation qhia txog qhov mob ntawm lub qhov muag tau lees paub raws li lub ntiaj teb (Fig.4F ~ 4I) thiab GS immunoreactivity (Fig.4K ~ 4N), feem. Lub zos ntawm Ibal nyob rau hauv microglia yog heev tsawg nyob rau hauv ib txwm thiab CFA pawg ( xub xub hauv daim duab 4F, 4G, raws li). Kev ua kom microglia yog inhibited nyob rau hauv EAU nas ( xub taub hau hauv Fig.4H) los ntawm kev kho betaine (Fig.4I, 4J). GS-zoo immunoreactivity tshwm sim zoo ib yam li lub ntiaj teb no nyob rau hauv lub retina (Fig.4K ~ 4N). Activated Müller hlwb hauv EAU ntxiv rau pawg tsheb muaj qis dua GS-immunoreactivity theem (Fig. 40).

Betaine suppressed adhesion molecule thiab pro-inflammatory mediators hauv EAU

Tom ntej no, peb tshuaj xyuas qhov adhesion molecule qhia siv PCR real-time (Fig. 5A). Kev txo qis hauv vascular cell adhesion molecule 1 (VCAM1) mRNA qib hauv EAU ntxiv rau Betaine pawg tau pom (p<0.05 vs.eau+vehicle).="" the="" mrna="" levels="" of="" serpina3n,interleukin-1β(il-1β),="" tumor="" necrosis="" factor-alpha="" (tnf-a),="" inducible="" nitric="" oxide="" synthase(inos),="" and="" cyclooxygenase="" at-2(cox-2)as="" pro-inflammatory="" mediators,="" were="" assessed="" to="" confirm="" the="" inflammatory="" condition="" (fig.="" 5b).="" the="" mrna="" levels="" of="" serpina3n,="" il-1β,="" tnf-a,="" cox-2="" were="" significantly="" downregulated="" in="" the="" eau+betaine="" group="" compared="" with="" that="" of="" vehicle-treated="" eau="" group="" (fig.5b).="" these="" results="" indicate="" that="" the="" betaine="" treatment="" suppressed="" the="" upregulation="" of="" pro-inflammatory="">

Betaine upregulated cov antioxidant enzymes catalase (CAT) thiab SODinEAU

Txoj kev tshawb fawb txog qib oxidative puas tsuaj hauv cov ntshav tau ua rau peb tshawb xyuas cov tshuaj tiv thaiv antioxidant ntawm cov enzymes antioxidant, suav nrog CAT, SOD1, SOD2, thiab SOD3 (Fig.5C). Peb tau soj ntsuam cov kev qhia tawm ntawm CAT, SOD1, SOD2, thiab SOD3 nyob rau hauv lub qhov muag ntawm EAU ntxiv rau Betaine pab pawg sib piv nrog EAU ntxiv rau pawg tsheb.

Betaine qhib txoj hauv kev Keapl-Nrf2

Txhawm rau txhawb kev tiv thaiv oxidative nyhuv ntawm betaine, txoj kev Keapl-Nrf2 tau kuaj xyuas (Fig. 6). Cov protein ntau ntawm Keapl (0.75±0.05 quav hloov, p<0.05,fig.6a)and nrf2(0.79±0.04fold=""><0.05,fig.6b)in eau+vehicle="" group="" were="">

piv nrog rau kev tswj ib txwm. Ntawm qhov tod tes, Keapl thiab Nrf2 tau pom 1.46±0 00 fold hloov lossis 1.13±0.34 fold hloov pauv rau cov ntawm EAU plus Vehide pawg (p<0.01 and=""><0.001,>

Kev sib tham

Qhov no yog thawj txoj kev tshawb fawb qhia tias betaine mitigates qhov kev loj hlob ntawm EAU pathogenesis los ntawm kev tiv thaiv inflammatory thiab anti-oxidant los, tab sis tsis yog los ntawm suppressing T cell proliferation (Schematic illustration nyob rau hauv Fig.7).

Kev tswj hwm cov txiaj ntsig ntawm betaine hauv cov kab mob autoimmune raws li pov thawj siv EAU, tus qauv ntawm tus kab mob autoimmune, yog xav tias yog vim qhov txo qis ntawm oxidative kev nyuaj siab thiab cov neeg kho mob pro-inflammatory, tab sis tsis yog T cell proliferation, los ntawm betaine [19]. Ib yam li ntawd, txoj kev tshawb fawb tam sim no tau qhia tias betaine tsis cuam tshuam rau T cell proliferation thiab cytokine profile hauv kab lis kev cai supernatant hauv EAU qauv, qhia tias betaine tsis cuam tshuam rau lub cev tiv thaiv kab mob ntawm kev loj hlob ntawm autoimmune T hlwb hauv EAU. Lub uvea yog lub hom phiaj lub cev hauv EAU. Lub uvea thiab retina yog cov kab mob tiv thaiv kab mob uas tsis muaj lymphatics [20]. Lub autoimmune T hlwb nyob rau hauv EAU yog invaded ntawm ib ceg ntawm ciliary thiab ophthalmic hlab ntsha [21]. Oxidative stress yog ib qho tseem ceeb taw qhia rau qhov kev loj hlob ntawm inflammatory teb thiab ntau reactive oxygen hom ua rau endothelial dysfunction thiab cov ntaub so ntswg raug mob [22]. Cov kab mob endothelial cuam tshuam ua rau kev nce qib ntawm cov kab mob inflammatory thiab inflammatory molecules [22]. Inflammatory mediators thiab hlwb nyob rau hauv lub uvea yog tshwm sim nyob rau hauv lub retinal pigment epithelial hlwb, uas cuam tshuam cov junctions ntawm pas nrig thiab cone hlwb thiab pigmented epithelial hlwb, ua rau ib tug detached retina [23]. Lub cev ciliary yog qhov chaw nkag rau ocular ocular. Cov kab mob retina feem ntau koom nrog hauv kev ua kom cov neeg nyob hauv microglia thiab infiltration ntawm cov hlwb inflammatory vim yog kev tawg ntawm cov ntshav-retina barrier [24]. Nyob rau hauv cov mob neuropathological, nrog rau cov qog hlwb [25], axotomy [26], thiab tus kab mob kis tau tus kab mob [27], activated macrophages thiab microglia tau txawv los ntawm Ibal. Tsis tas li ntawd, cov neeg nyob hauv lub microglia tau koom nrog hauv cov kev hloov pauv pathological tshwm sim hauv cov kab mob retinal degenerative thiab tso cov inflammatory mediators uas exacerbate tus kab mob txheej txheem [28]. Cov txiaj ntsig no qhia tias betaine tawm dag zog los tiv thaiv kev mob hauv uvea thiab ciliary lub cev, lub hom phiaj tseem ceeb ntawm EAU, thiab tuaj yeem txo cov kev ntxhov siab oxidative hauv cov ntshav. Txawm li cas los xij, qhov tseeb mechanism tseem yuav tau kawm.

Activated microglia yog lub hauv paus tseem ceeb ntawm pro-inflammatory cytokines nyob rau hauv retinal degenerative mob [29]. Pro-inflammatory cytokines, suav nrog ILs thiab TNF, muaj feem cuam tshuam nrog ocular o [30] thiab retinitis [6,29]. Dhau li ntawm microglia, Müller hlwb tau qhib rau hauv txhua qhov xwm txheej pathological uas tshwm sim hauv retina [31]. Activated Müller hlwb koom nrog hauv cov nyhuv neuroinflammatory hauv lub retina los ntawm kev sib txuas thiab tso tawm cov kab mob ntsig txog cov kab mob [31]. Peb postulate tias betaine mitigates inflammatory teb nyob rau hauv EAU-induced nas los ntawm suppressing lub activation ntawm microglia thiab Müller hlwb. Lub upregulation ntawm VCAMl yog heev koom nyob rau hauv lub infiltration ntawm inflammatory cells [32].VCAMl yog expedited rau CD4 Tlym-phagocytes los ntawm kev sib tham nrog lig antigen-4[3].Ntxiv, Serpina3n, ib tug enzyme uas pib. o [34], tau kuaj pom nyob rau hauv Müller hlwb, astrocytes, thiab retinal pigment epithelia ntawm lub teeb puas retinas [35] thiab muaj ntau yam txawv txav nyob rau hauv lub Nrl'mouse retina nrog impaired cone hlwb [36].Serpina3n yog nce nyob rau hauv EAU cov nas uas muaj qhov txhab mob loj heev tab sis txo qis hauv betaine-kho EAU pawg. Ib qho kev tshawb pom zoo sib xws tau tshaj tawm rau tus mob schizophrenia nrog neuroinflamation [34], raws li murine Serpina3n yog ib qho orthologue ntawm tib neeg Serpina3 [37]. Tsis tas li ntawd, kev nce hauv IL -1 tau pom nyob rau hauv siab fructose-induced retinal raug mob [38]. Peb tshaj tawm tias cov tshuaj tiv thaiv kab mob ntawm betaine cuam tshuam nrog kev tswj hwm qis ntawm VCAM1, Serpina3n, thiab IL-1 hauv EAU-induced nas. Txoj kev Keep-Nrf2 yog siv los saib xyuas oxidative stress [39]. Betaine tau paub tias yog cov tshuaj tiv thaiv oxidant molecule, uas tau cuam tshuam nrog Keapl-Nrf2 txoj hauv kev hauv acetaminophen-induced mob siab mob siab qauv [40]. Tsis tas li ntawd, cov kab mob siab gene qhia profile tau ua tiav tom qab 3H-1, 2-dithiole-3-thione kev kho mob, muaj lub luag haujlwm ntawm kev txhim kho cov tshuaj tua kab mob carcinogens thiab tiv thaiv neoplasia [4]. Qhov tshwm sim ntawm qhov profileing no tau qhia tias Keap1-Nrf2 tswj nrf2-dependent 3H-1,2-dithiole-3-thione-inducible noob, suav nrog AF033381, raws li betaine homocysteine ​​methyl transferase, tau nce ntxiv, thiab koom nrog rau kev tshem tawm thiab tiv thaiv oxidation [41]. Cov lus teb inflammatory hauv EAU raug ntxias los ntawm infiltration ntawm inflammatory hlwb, xws li T hlwb thiab macrophages [42], thiab zus tau tej cov oxidative kev nyuaj siab, tshwj xeeb tshaj yog nyob rau hauv photoreceptor mitochondria ntawm thaum ntxov theem [43]. Raws li cov txiaj ntsig no, kev kho betaine yog tus neeg sib tw los daws qhov EAU-vim cov ntaub so ntswg puas tsuaj los ntawm kev hloov kho ntawm Keap1-Nrf2 txoj hauv kev, yog txoj hauv kev tseem ceeb rau kev tswj hwm ntawm oxidative kev nyuaj siab.

Cov nyhuv antioxidant ntawm betaine tau raug soj ntsuam dav dav hauv cov qauv kev raug mob ntawm cov radical-induced [44] .Nyob rau hauv levodopa-induced oxidative-kev puas hlwb hlwb, betaine tau txhim kho rau qib ntawm CAT thiab SOD, uas yog cov sawv cev antioxidant enzymes [4]. SOD1, SOD2, thiab SOD3 yog qhib los ntawm cov txheej txheem sib txawv thiab nyob rau hauv lub cytoplasm, mitochondria, thiab extracellular matrix, feem [45]. Betaine, raws li kev tiv thaiv oxidative molecule, yog koom nrog hauv kev txo oxidative puas tsuaj [46]. Qhov txo qis oxidative kev ntxhov siab tau txuas ntxiv los daws qhov mob, qhia los ntawm Ibal-zoo macrophages / microglia hauv ntau cov kab mob, suav nrog Alzheimer's kab mob, Parkinson's disease, thiab ntau yam sclerosis [47]. Kev kho betaine tau raug tswj hwm mus rau mRNA qib ntawm oxidative stress marker, piv nrog cov hauv EAU ntxiv rau pawg tsheb. Qhov txiaj ntsig no txhais tau hais tias kev kho betaine txo oxidative kev nyuaj siab hauv cov hlab ntsha tsis cuam tshuam nrog T cell proliferation hauv lub cev tiv thaiv kab mob ntawm tus nas EAU qauv.

Ua ke, txoj kev tshawb fawb tam sim no qhia tias betaine tuaj yeem txo qhov mob hauv cov retinas thiab ciliary lub cev ntawm EAU-induced nas, tejzaum nws los ntawm kev tiv thaiv oxidation thiab tiv thaiv kab mob.

Tsab ntawv xov xwm no yog muab los ntawm https://doi.org/10.5607/en21011