Kev sib raug zoo ntawm Xanthine Oxidoreductase Kev Ua Haujlwm Thiab Aristolochic Acid Induced Nephropathy

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

PART Ⅱ: Cov qog xanthine oxidoreductase kev ua haujlwm hauv nas qauv ntawm aristolochic acid nephropathy

Takeo Ishii, Tomohiro Kumagae, Hiromichi Wakui, Shingo Urate, Shohei Tanaka & et al.

Xanthine oxidoreductase(XOR) yog ib qho tseem ceeb enzyme hauv purine metabolism thiab uric acid ntau lawm, thiab nws cov qib tau tshaj tawm tias yuav nce ntxiv thaum muaj kev ntxhov siab, yog li txhawb lub cev puas tsuaj. Ntawm no, peb tau tshawb xyuas cov haujlwm ntawm XOR(Xanthine oxidoreductase)nyob rau hauv tus qauv nas ntawmaristolochic acid (AA) induced nephropathy, ib hom kab mob nephrotoxic chronic raum (CKD). Kev txo qis hauv lub raum ua haujlwm tau pom nyob rau hauv nas mus txog 4 lub lis piam tom qab 4 lub lis piam ntawm AA (aristolochic acid) (2.5 mg kg') kev tswj hwm. Lub raum histology qhia txog qhov nce hauv tubular interstitial fibrosis dhau sijhawm. Txawm tias AA(aristolochic acid)kev tswj hwm tsis hloov XOR(Xanthine oxidoreductase)kev ua haujlwm hauv plasma, plawv, siab, lossis nqaij, XOR(Xanthine oxidoreductase)kev ua haujlwm tau nce ntxiv hauv lub raum cov ntaub so ntswg. Peb cov txiaj ntsig tau qhia tias lub raum cov ntaub so ntswg tshwj xeeb nce hauv XOR (Xanthine oxidoreductase) kev ua haujlwm yog koom nrog hauv kev loj hlob ntawm tubulointerstitial mob, tshwj xeeb yog fibrosis.

Cistanche extract kho mob raum zoo

NYEM QHOV NO RAU PART Ⅰ

Kev sib tham

Cov txiaj ntsig ntawm kev tshawb fawb tam sim no tau pom tias lub raum XOR(Xanthine oxidoreductase)Kev ua haujlwm tau txhim kho, nrog rau kev txhim kho lub raum tsis ua haujlwm thiab fibrosis hauv AA(aristolochic acid)nephropathy nas qauv. Intriguingly, lub raum XOR(Xanthine oxidoreductase)kev ua haujlwm tau txhim kho kom ruaj khov txawm tias tom qab AA(aristolochic acid)Kev txhaj tshuaj, uas tuaj yeem koom nrog hauv kev tsim lub raum mus ntev fibrosis hauv AA(aristolochic acid)nephropathy. AA(aristolochic acid)yog muab tso rau hauv tubular epithelial hlwb ntawm cov organic anion transporter 1 (OAT1) channel qhia ntawm lub raum tubular hauv qab daim nyias nyias [28,29]. Tom qab AA(aristolochic acid)kev tswj hwm, cellular cyclin B1 qib nce, muaj kev cuam tshuam ntawm lub voj voog ntawm tes ntawm tubular epithelial hlwb ua ntej mitosis, thiab apoptosis tshwm sim tsis tu ncua [30]. Cov txheej txheem no yog vim li cas qhov no AA(aristolochic acid)nephropathy qauv yog lub raum tshwj xeeb thiab muaj txiaj ntsig zoo rau kev tshawb xyuas cov txheej txheem ntawm lub raum fibrosis. Peb tsis tau kuaj cov nas hnub nyoog qis dua 12 lub lis piam; Txawm li cas los xij, cov nas no yuav zoo li muaj cov qauv zoo sib xws ntawm lub raum tubular epithelial cell apoptosis thiab hauv qab daus daim nyias nyias. Txawm li cas los xij, nws tsis paub tias puas yog epithelial cell turnover yog qhib kom nrawm dua hauv cov nas me. Tubular epithelial cell apoptosis ua rau lub voj voog ntawm tes raug ntes ntawm peritubular capillary (PTC) network, uas ua rau tag nrho cov nephron ua hypoxic, yog li ua rau kev qhia ntawm HIF-1 . OAT1 channel feem ntau muaj nyob rau ntawm tubular epithelial hauv qab daus daim nyias nyias ntawm lub raum tab sis kuj tseem muaj nyob rau hauv me me hauv daim siab hlwb [28]. Peb cov txiaj ntsig tau pom tias, ua raws li AA(aristolochic acid)Administration, XOR(Xanthine oxidoreductase)activation mas tshwm sim nyob rau hauv ob lub raum thiab tsis tau pom nyob rau hauv lwm cov ntaub so ntswg. Sun et al.[31] soj ntsuam PTC ntom ntom nrog rau HIF-1a thiab vascular endothelial growth factor (VEGF) qhia hauv poj niam nas uas tau noj AA(aristolochic acid)ob zaug ib hnub rau yim lub lis piam. Lawv pom tias PTC tsawg zuj zus nyob rau lub sijhawm, nce HIF-1a thiab VEGF, thiab tsis muaj kev txhim kho hauv VEGF qhia.Sun et al. xaus lus tias AA(aristolochic acid) Kev kho kom haum xeeb txo qis hauv PTC network ua rau HIF ntau dua -1o qib qhia.

Hauv kev tshawb fawb tam sim no, AA(aristolochic acid)kev tswj hwm ua rau lub cev poob qis, nrog rau lub raum tsis ua haujlwm. Qhov qis ntawm lub cev qhov ntsuas yog txuam nrog kev tuag ntau dua hauv cov neeg mob CKD. Uremic cachexia paub tias yog qhov ua rau poob phaus hauv CKD, cuam tshuam nrog acidosis thiab o. Ntxiv rau, cov neeg mob CKD feem ntau muaj sarcopenia, uas cuam tshuam txog kev pheej hmoo ntawm kev tuag thiab mob plawv. Txawm hais tias peb tsis tau tshuaj xyuas nas cov zaub mov noj thiab cov leeg nqaij pob txha hauv txoj kev tshawb no, AA(aristolochic acid) induced yuag poob yuav tshwm sim los ntawm cachexia thiab sarcopenia. Cachexia tshwm sim los ntawm uremia tau pom zoo kom txo cov khoom noj thiab lub cev hnyav. Ntawm qhov tod tes, qhov nce hauv adipogenesis thiab lipogenesis uas tshwm sim concomitantly nrog nce hauv XOR.(Xanthine oxidoreductase)kev ua haujlwm, ntsig txog C / EBP lossis PPARy thiab SREBF1 gene qhia kev nce qib, qhia tias cov tshuaj tiv thaiv no yog kev tiv thaiv kev poob phaus.

Peb kuj pom tias AA(aristolochic acid)kev tswj xyuas tas li nce qib ntawm HIF-1 qhia, yuav yog vim cov ntaub so ntswg tawg. Ua ke, cov txiaj ntsig no qhia tias nephron hypoxia thiab nce hauv XOR(Xanthine oxidoreductase)tej zaum coincide. Kev ua siab ntev nce qib ntawm XOR(Xanthine oxidoreductase)hauv lub raum cov ntaub so ntswg tau tshwm sim los ntawm AA(aristolochic acid) induced apoptosis ntawm tubular epithelium. Cov ntaub so ntswg hypoxia coj mus rau qhov tawg ntawm ATP, yog li ua kom XOR(Xanthine oxidoreductase). XOR elevated(Xanthine oxidoreductase)Kev ua haujlwm tau pom tsis tsuas yog nrog ATP tawg, tab sis thaum lub sij hawm cov ntaub so ntswg puas los ntawm ROS ntau lawm. Kev tshawb nrhiav ntxiv yog yuav tsum tau txiav txim siab seb XOR(Xanthine oxidoreductase)provoked tssue kev puas tsuaj los ntawm kev tsim cov oxidative kev nyuaj siab. XOR(Xanthine oxidoreductase)yog tus nqi-txheej enzyme hauv purine metabolism. Nws tsim uric acid thiab ROS, tom kawg uas ua rau oxidative kev nyuaj siab.

Los ntawm ROS ntau lawm, proinflammatory cytokines nyob rau hauv NLR tsev neeg pyrin domain uas muaj 3 (NLRP3) inflammasome/IL-1 txoj kev yog stimulated nyob rau hauv macrophages [32].Meanwhile, NRLP3 / IL-1 txoj kev kuj tau qhib los ntawm monosodium urate, uas exacerbates lub raum tsis ua hauj lwm los ntawm cov ntaub so ntswg deposition ntawm uric acid crystals [32-34]. Yisireyili li al.(Xanthine oxidoreductase). Page et al[36] soj ntsuam XOR(Xanthine oxidoreductase)Kev ua haujlwm tshwm sim los ntawm inflammatory cytokines hauv tib neeg mammary epithelial hlwb. XOR(Xanthine oxidoreductase)Kev ua haujlwm feem ntau tau nce ntxiv thaum kho nrog IFN-y, tab sis tsis muaj kev cuam tshuam nrog IL-6. Fibrosis yog suav tias yog kev nce qib los ntawm kev txhim kho kev txhawb nqa ntawm TGF- txoj hauv kev los ntawm transglutaminase hom 2 (TG2), uas txhawb nqa collagen I-IV kev qhia hauv cov khoom siv nuclear kappa lub teeb saw txuas ntxiv ntawm cov hlwb B (NF-kB)[{{7} }]. Thaum kawm AA(aristolochic acid)nephropathy nyob rau hauv nas nrog C57BL / 6 keeb kwm yav dhau, Scarpellini li al. [41 qhia tias syndecan-4, uas txhawb nqa fibrosis, externalizes TG2 rau cell membrane. Qhov no tshwm sim hauv kev tsim cov complex nrog TGF- thiab ua rau muaj kev loj hlob ntawm lub raum fibrosis. Cov nyhuv no tau txo qis hauv syndecan-4 cov nas nas. Cov proteasome inhibitor bortezomib tau tshaj tawm tias inhibit fibrosis los ntawm TGF- inhibition [30] .TGF- plays lub luag haujlwm tseem ceeb hauv fibroblast transformation hauv AA(aristolochic acid)nephropathy los ntawm fibrotic mechanism [4]. Hauv peb AA(aristolochic acid)study, TGF- and XOR(Xanthine oxidoreductase)tau qhia ib txhij-taneously, tab sis qhov no fibrotic mechanism yog feem ntau yuav induced los ntawm TGF- qhia ntawm activated XOR(Xanthine oxidoreductase). Kev qhia ntawm TGF- thiab Col I noob tau nce hauv kev teb rau kev kho mob nrog AA(aristolochic acid), uas qhia txog kev ua haujlwm fibrotic. Tsis tas li ntawd, qhov kev qhia ntawm HIF-la, ib feem ntawm hypoxia inducible factor, nce concurrently nrog XOR.(Xanthine oxidoreductase)Kev ua kom muaj zog hauv txoj hauv kev fibrotic, uas ua rau muaj kev ntxhov siab oxidative hauv cov ntaub so ntswg.

Qhov kev tshawb pom ntawm qhov kev sim no qhia tau hais tias kev tsim cov pa oxygen reactive (ROS) thaum ua kom NADPH oxidase tshwm sim nrog XOR.(Xanthine oxidoreductase)Kev ua kom ua rau cov ntaub so ntswg necrosis tshwm sim los ntawm cov ntaub so ntswg hypoxia, ua raws li kev loj hlob mus rau txoj kev fibrotic. Tsis tas li ntawd, cov kev soj ntsuam microscopic pom tias XOR.(Xanthine oxidoreductase)kev ua haujlwm thiab thaj chaw fibrotic tau sib raug zoo (Daim duab 6C), qhia tias XOR(Xanthine oxidoreductase)tej zaum yuav ua rau ib nrab tssue puas. Txawm li cas los xij, yuav tsum tau kuaj xyuas ntxiv.

Nws tau raug taw qhia tias XOR(Xanthine oxidoreductase)tuaj yeem tswj hwm adipogenesis thiab mesenchymal hloov pauv hauv lub raum tubule epithelium [42]. Txawm li cas los xij, nws tsis tau qhia meej tias XOR(Xanthine oxidoreductase)noob tsis zoo tswj cov adipose droplet deposition thiab mesenchymal transformation, los yog lawv tshwm sim los ntawm xanthin deposition nyob rau hauv lub raum tssue thaum XOR(Xanthine oxidoreductase)yog depleted. Peb tsis tau tshawb xyuas cov txheej txheem lipid hauv cov ntshav, tab sis peb txoj kev tshawb fawb tau pom tias cov kev hloov pauv hauv lub raum cov ntaub so ntswg yog apoptosis, poob ntawm tubular epithelial hlwb, thiab fibrosis. Lipid droplet deposition tsis tau qhia. Hauv no AA(aristolochic acid)qauv, adipogenesis thiab lipogenesis nce ntxiv nrog XOR(Xanthine oxidoreductase)kev ua haujlwm, tsis sib xws rau XOR(Xanthine oxidoreductase)qauv. Cov txiaj ntsig no tau qhia tias qhov adipogenesis thiab lipogenesis uas tshwm sim nrog C / EBP lossis PPARy thiab SREBF1 kev loj hlob ntawm noob yog qhov tshwm sim ntawm cachexia lossis mob tshwm sim los ntawm ROS, thiab tsis ua haujlwm ntawm XOR.(Xanthine oxidoreductase)ncaj qha.

Chen et al[43] qhia tias XOR(Xanthine oxidoreductase)kev ua haujlwm tau txo qis hauv C / EBP uas ntsiag to hlwb; Yog li ntawd, C/EBP noob nyob rau ntawm XOR(Xanthine oxidoreductase)noob. Tsis tas li ntawd, hauv ob/ob nas qauv, XOR(Xanthine oxidoreductase)noob depletion tau pom los inhibit adipogenesis; raws li qhov no, XOR(Xanthine oxidoreductase)puas raug suav hais tias yog dag ntawm PPAR? noob. XOR(Xanthine oxidoreductase)yog pom zoo raws li kev kho lub hom phiaj ntawm metabolic syndrome nrog hyper uricemia. Hauv peb AA(aristolochic acid)qauv, PPARy, C / EBP, thiab SREBFl cov noob qhia tau nce siab nrog XOR(Xanthine oxidoreductase)kev ua si. Cov txiaj ntsig no qhia tias XOR(Xanthine oxidoreductase)activated adipogenesis los yog lipogenesis, los yog, conversely, uas cachexia los yog oxidative kev nyuaj siab tshwm sim los ntawm AA(aristolochic acid)ua rau kev ua kom cov adipogenetic los yog lipogenetic noob raws li kev tiv thaiv mechanism; ntxiv kev tshawb nrhiav yog xav tau ntawm qhov no. Kev tswj hwm AA(aristolochic acid)ua rau apoptosis thiab nephron hypoxia nrog elevated HIF -1 qhia, thiab induced kev loj hlob mus rau fibrotic txoj kev los ntawm TGF- thiab Col 1. XOR(Xanthine oxidoreductase)yog induced tsuas yog los ntawm hypoxia nrog oxidative kev nyuaj siab, ntxiv xav tias yuav tsim ROS los ntawm kev nce qib ntawm NADPH oxidase, qhia tias XOR(Xanthine oxidoreductase)koom nrog hauv cov txheej txheem fibrotic. Kev tshawb nrhiav ntxiv ntawm cov txheej txheem no yuav tsum tau qhia meej seb puas yog adipogenesis thiab lipogenesis raug ntxias los ntawm XOR(Xanthine oxidoreductase)los yog nce raws li qhov tshwm sim ntawm cov ntaub so ntswg puas. Qhov kev txwv tseem ceeb ntawm txoj kev tshawb no yog cov pab pawg me me. Txawm li cas los xij, peb tau pom qhov sib txawv ntawm cov cim tau soj ntsuam, qhia tias kev tshawb nrhiav ntxiv ntawm cov kev pabcuam kho mob tau lees paub. Cov kev tshawb fawb ntxiv yuav tsum ntsuas qhov cuam tshuam ntawm XOR(Xanthine oxidoreductase)inhibition hais txog kev txo qis ntawm fibrosis hauv cov kab mob hauv lub raum. Lwm qhov kev txwv yog tias peb tsis tau soj ntsuam cov ntshav lipid mechanism kom meej thiab tsis tuaj yeem ntsuas cov ntshav lipid metabolic marker. Txawm li cas los xij, qhov kev hloov pauv loj hauv lub raum cov ntaub so ntswg yog apoptosis, qhov poob ntawm cov tubular epithelial hlwb, thiab fibrosis, thaum lipid droplet deposition tsis pom. Tsis tas li ntawd, peb tau soj ntsuam adipogenesis thiab lipogenesis lub raum cov noob qhia, uas tso cai rau peb ntsuas lipid metabolism hauv qab AA.(aristolochic acid)kev tswj hwm. Hauv no AA(aristolochic acid)qauv, adipogenesis nce zuj zus nrog XOR nce(Xanthine oxidoreductase)kev ua haujlwm, sib piv rau qhov tau pom hauv XOR(Xanthine oxidoreductase)qauv. Cov txiaj ntsig no qhia tias XOR(Xanthine oxidoreductase)tsis muaj kev tiv thaiv ncaj qha rau ntawm lub raum cov ntaub so ntswg, thiab qhov tseeb tias adipogenesis uas tshwm sim nrog C / EBPo lossis PPARY thiab SREBF1 cov noob qhia txog kev loj hlob tshwm sim los ntawm kev mob tshwm sim los ntawm ROS qhia tias cov tshuaj tiv thaiv adipogenetic lossis lipogenetic yog kev tiv thaiv.

Hauv kev xaus, cov txiaj ntsig ntawm kev tshawb fawb tam sim no pom tias cov ntaub so ntswg XOR(Xanthine oxidoreductase)Kev ua haujlwm, tshwm sim los ntawm cov ntaub so ntswg hypoxia induced catabolism, tau ua haujlwm tsis tu ncua hauv AA(aristolochic acid) induced nephropathy CKD qauv. Tsis tas li ntawd, lub raum tshwj xeeb XOR(Xanthine oxidoreductase)Kev ua kom muaj feem cuam tshuam nrog kev puas tsuaj ntawm lub cev thiab lub raum fibrotic lesion kev loj hlob. Yog li, qhov no AA(aristolochic acid)nephropathy qauv tuaj yeem pab tau los tshawb xyuas ntxiv txog kev tiv thaiv kev tiv thaiv XOR(Xanthine oxidoreductase) mediated lub raum fibrotic hloov ua rau lub raum kab mob kawg.

kuaj rau flavonoids

Cov ntaub ntawv

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Lus Cim: Cov tshuaj suav tshuaj suav tshuaj ntsuab cistanche (tseem hu ua "daj tshuaj ntsuab" thiab "tso suab puam ginseng"), loj hlob tsuas yog hauv cov suab puam qhuav thiab sov. Raws li ib qho ntawm cuaj cov tshuaj tsis txawj tuag, Cistanche (cistanche tubulosa / cistanche deserticola / desertliving cistanche / cistanche salsa) cov ntsiab lus nrog cov khoom xyaw nplua nuj xws li echinacoside, acteoside, tag nrho phenylethanoid glycosides, flavonoids, polysaccharides, thiab lwm yam. nourishing tshuaj ntsuab thiab khoom noj khoom haus rau tib neeg lub cev tiv thaiv kab mob, cov kab mob hauv nruab nrog cev, thiab hlwb hlwb thiab neurons, thiab lwm yam. Cov kev tshawb fawb tshuaj niaj hnub no tau lees paub cov txiaj ntsig ntawm cistanche (cov txiaj ntsig ntawm cistanche): txhim kho kev tiv thaiv; txhim kho kev ua haujlwm ntawm kev sib deev thiab lub raum ua haujlwm; tiv thaiv qaug zog; anti-aging; txhim kho kev nco; anti-Parkinson tus kab mob; anti-Alzheimer tus kab mob; antioxidation; yooj yim- cem quav; anti-inflammatory; txhawb cov pob txha loj hlob, ua kom tawv nqaij dawb; tiv thaiv daim siab; lwm.