Ursodeoxychico Acc Prodications, tseem hu ua 3a, {7 -} dihydroxy-5 -}}}}}} organic compound. Molecular Cov Qauv C24h40O4, CAS 128-13-2, hmoov dawb, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw, tsw Soluble hauv ethanol, insoluble hauv chloroform; Yooj yim soluble hauv glacial acetic acid thiab soluble hauv sodium hydrocide tov. Kho kom meej, nws yog siv los ua kom muaj kev tso pa tawm ntawm cov kua txiv hmab txiv ntoo thiab cov roj cholesterol thiab cov roj cholesterol thiab cov roj cholesterolly hauv cov roj av roj av. Cov khoom siv tshuaj ntawm cov tshuaj no haum rau lub gallbladder cholesoles roj, uas yuav tsum muaj lub pob zeb uas tuaj yeem nkag los ntawm cov xoo hluav taws xob, thiab lub zais pa tsis sib haum yuav tsum yog ib txwm; Cholestasis ntsig txog tus kab mob siab (xws li thawj zaug hauv paus bilhrhosis); Bile Reflux Gastritis.
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Tshuaj Cov Qauv |
C24H40O4 |
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Muaj pes tsawg leej |
392 |
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Molecular hnyav |
393 |
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m/z |
392 (100.0%), 393 (26.0%), 394 (2.7%) |
|
Kev Ntsuam Xyuas |
C, 73.43; H, 10.27; O, 16.30 |
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Pharmacology thiab Toxicology
So kom txaus lubdi sphincter leeg muaj cov nyhuv choleretic.
Txo cov siab rog, nce kev ua si ntawm daim siab peroxidase, txhawb kev txuam nrog lub siab glycogen, thiab txhim kho lub siab muaj peev xwm tiv taus thiab detoxify.
Nws tuaj yeem txo cov kev xav ntawm triglycerides hauv daim siab thiab ntshav.
Inhibit lub recordion ntawm cov zom zom mov thiab cov kua txiv digestive.
Kev tshawb fawb txawv teb chaws kuj tau pom tias ursodeoxycholic acid tau cuam tshuam nrog cov kab mob HLIION rau cov neeg sim siab thiab txo tus lej ntawm kev qhib t hlwb. Ursodeoxychocic acid tau zoo dua nyob rau hauv cov roj cholesterol
Kho Mob Mob Kab Mob Kab Mob Kab Mob
Ursodeoxychico Acc Prodications(3, {{{7 -}}}-5 -} Cholic acid, UDCA) yog cov nyiaj ua ntej rau 3% ntawm tag nrho tib neeg bile. Nws tau ua ntej tau ua ntej tom qab Showa los ntawm Okayama University hauv Nyiv, uas cais nws los ntawm Suav Xyooj Npib. Xyoo 1985, Luschner li al. Pom ib qho kev txo qis hauv cov ntshav siab transaminase thaum siv nws los kho cov gallstones nrog kab mob siab. Tom qab, ntau cov kev tshawb fawb cov kev tshawb fawb tau lees tias UDCA muaj cov nyhuv tseeb rau qee cov kab mob siab. Cov txheej txheem ntawm kev nqis tes ua thiab kho cov nyhuv yog qhia luv luv raws li hauv qab no:
1. Mechanism ntawm Kev Ua
Cholestasis ntxias cov kab mob siab yog txuam nrog kev sib txuam ntawm chenodeoxychocic acid, thiab lithochhokic acid, thiab cov kua qaub ua kom ua rau lawv cov nyhuv descaling. UDCA yog qhov tsis yog - pakic bile acid uas muaj kev sib tw ntawm cov kua txob lom zem kawg hauv cov acids ileum. Los ntawm kev ua kom lub teeb liab network tsim los ntawm calcium ions thiab protein kinase cile accids nyob rau hauv cov ntshav thiab daim siab ntawm lub siab, ua tiav cov nyhuv ntawm anti bile stasis. UDCA tuaj yeem sib tw hloov cov kua txob lom me ntsis cov molecules ntawm cov kab mob cell thiab cov kab mob bile cells los ntawm kev puas tsuaj los ntawm ntau toxic bile acids.
Cov kev cuam tshuam saum toj no tau qhia tshwj xeeb hauv:
(1) kev tiv thaiv cellular tiv thaiv.
Udca complexes tuaj yeem txo qis cov lysis cell tsim los ntawm hydrophobic bile acids nyob rau hauv lub siab acids nyob rau hauv kev coj noj coj ua tus nas thiab tus neeg mob siab.
(2) membrakas stabilization nyhuv.
Udca tuaj yeem tiv thaiv kev hloov pauv ntawm Mitochondrial membrane kev ua txhaum los ntawm cov kua tsib me me, thiab cov nqaij npuas me me uas nws tuaj yeem ua rau muaj cov roj ntsha lom los ntawm membrane stabilization.
(3) antioxidant nyhuv.
UDCA tuaj yeem tiv thaiv kev ua kom zoo ntawm kupffer hlwb tshwm sim los ntawm cov kua txob lom, nce cov protein hauv daim siab ntawm daim siab thiab oxidative kev puas tsuaj rau daim siab hlwb.
(4) Cov kev txhim kho tsis muaj zog tiv thaiv kab mob.
Udca tsis ncaj ncees txwv tsis pub cuam tshuam txog cov nyhuv stimulating ntawm hydrophobic bile acids thiab ncaj qha suppresses cov kev qhia ntawm horcocompatibility txoj cai (MHC) chav kawm thiab kev ua haujlwm zoo Glucocorticoid cov khoom plig.
2. Cov ntawv thov kho mob
Thawj cov menyuam hauv qab phais mob cirrhosis (PBC). PBC yog tus mob siab ntev ua tus kab mob siab uas tsis muaj mob hlwb Pares li al. Ua ib qho kev sim ua ke nrog nruab nrab ntu ntawm 45 xyoo ntawm biopsies.Ursodeoxychico Acc ProdicationsTau pom tias UDCA tuaj yeem tiv thaiv qhov kev loj hlob ntawm keeb kwm ntawm pbc. Xyoo 1999, Angulo li al. Tshaj tawm tias nyob rau hauv ntev - Kev Kho Mob Tawv (nruab nrab ntawm cov neeg mob cirrhotict pbc Hauv feem ntau UDCA kev sim kev kho mob UDCA, siv tshuaj ntau npaum li cas yog 13-15 milligrams ib phaus ib hnub. Ob qho kev tshawb fawb tsis ntev los no tau tshawb pom qhov tsim nyog ntawm Udca tau pom tias koob tshuaj ntawm 13-15 ib hnub yog ua tau zoo dua li koob tshuaj ntawm 10-15 mg / kg lossis tsawg dua ib hnub. Kev ua tau zoo ntawm kev sib txuas nrog methotrexate lossis colchicine nyob rau hauv kev kho PBC yog tsis zoo dua los siv UDCA ib leeg; Tab sis thaum ua ke nrog prednisone lossis prednisone ntxiv azathioprine, nws txoj kev ua tau zoo rau kev txhim kho o yog qhov zoo dua li siv UDCA ib leeg.
Thawj sclerosing choolangitis (PSC). PSC yog tus mob tsis tshua muaj tus kab mob stenosis thiab dilation ntawm intraepatic thiab extraeepatic bile ducts. Lub sijhawm zoo kawg nkaus randomized placebo - tswj kev txhim kho tseem ceeb ntawm 22 xyoo (UDCA txhua hnub Tab sis rau pom tseeb bile du metrenosis, ntxiv UDCA rau endoscopic kev kho mob tuaj yeem txhim kho cov kev mob siab ntawm cov neeg mob.
Intraepatic cholestasis ntawm cev xeeb tub (ICP). ICP feem ntau tshwm sim hauv kev xeeb tub lig, nrog cov tsos mob tseem ceeb, uas tuaj yeem ua rau cov teeb meem yug ntxov ua ntej, tseem ua rau lub sijhawm yug menyuam. Nws ntseeg tau hais txog kev nce ntawm cov tshuaj estrogen hauv lub cev ntawm lub hauv paus ntawm cov noob caj noob ces. Randomized ob npaug- dig muag placebbo {}}}}} tswj kev kho mob UDCA rau IPC suav nrog 15 tus neeg mob. Cov pab pawg kho mob tau muab kev txhim kho hauv khaus thiab tawv nqaij biochemical ntsuas, thiab 8 tus poj niam cev xeeb tub (tau txais kev yug lossis ze rau lawv hnub kawg; Ntawm 7 tus poj niam cev xeeb tub tau kho nrog placebo, 5 yug tau 36 lub lis piam ntawm kev sib tw, suav nrog 1 tus neeg tseem ceeb. Tsis muaj niam lossis menyuam yaus cov kev mob tshwm sim tau pom thaum lub sijhawm kho. Yog li ntawd, UDCA kev kho rau ICP zoo li ua tau zoo thiab nyab xeeb.
GloLbladder fibricotic Liiver (cf). Colom Bo li al. compared UDCA treatment (15 mg/kg daily) with a placebo group after 1 year in a follow-up double-blind placebo-controlled trial involving 55 patients. Raws li qhov tshwm sim, nws tau pom tias pawg kho mob tau txhim kho tseem ceeb hauv cov tsos mob, thiab txhua hnub) tau ua haujlwm zoo dua li qis dua cov tshuaj (5-15 mg / kg txhua hnub).
Kev muaj kab mob siab C. hauv xyoo 2001, ob peb randomized placebo-}}}}}}}}}}}}}}}}} Kev sim ua ke nrog Alpha sib xyaw ua ke nrog Alpha sib xyaw ua ke. Qhov ntsuas tau biochemical tau txhim kho tom qab kev kho mob, tab sis kev tshem tawm tus kab mob siab (HCV)} {
Lwm yam. Cov kev tshawb fawb tau pom tias UDCA ua ke nrog Cyclosporine A thiab Methotrexate tuaj yeem tiv thaiv venous occlusion thiab}} Tus kab mob hostrus hauv kev kho mob pob txha ntawm heterotypic. Ib qho koob tshuaj txhua hnub ntawm 15 mg / kg Udca tuaj yeem txhim kho cov tsos mob intreasepatic cholesasis, thiab tag nrho cov kev noj niam txiv Atresia, thiab tag nrho cov kev noj haus etresia, thiab tag nrho cov kev noj niam txiv italia Kev tshawb fawb txog kev siv UDCA rau kev kho mob ntawm lwm daim ntawv cog lus kab mob, benign rov muaj tus kab mob sib luag,} eptimune muaj kev kub taub hau, thiab mob siab tawv.Ursodeoxychico Acc ProdicationsKev xav tau kev ua tau zoo ntxiv.
Neuroprotection thiab anti -} kev laus
Ursodeoxychico Acc Prodications, raws li ib txwm tshuaj rau kev kho lub siab thiab gloadbadder kab mob, tau nkag mus rau hauv lub sijhawm tsis ntev los no vim yog cov txiaj ntsig tsis ntev los no, cov txiaj ntsig tsawg) thiab cov txiaj ntsig zoo. Los ntawm kev tswj hwm mitochondrial ua haujlwm rau inhibiting neuroinflation, los ntawm kev tshem tawm cov kab mob metabolic, UDCA yog hloov pauv ntawm cov kab mob metabolic, UDCA yog hloov pauv ntawm cov kab mob metabolic, UDCA yog hloov pauv cov kab mob metabolic, UDCA yog hloov mus rau cov kab mob metabolic, UDCA yog hloov mus rau cov kab mob metabolic, UDCA yog hloov mus rau cov kab mob metabolic, UDCA yog hloov pauv ntawm cov kab mob metabolic, UDCA yog hloov mus rau cov kab mob metabolic, UDCA yog hloov pauv cov kab mob metabolic, UDCA yog hloov pauv cov kab mob metabolic, Hauv cov hauv qab no, los ntawm ob qhov tseem ceeb ntawm kev neuroProtection thiab anti -} Cov pov thawj nws lub peev xwm thiab cov pov thawj ua ntej.
Neuroproction: Mechisms los ntawm daim siab mus rau lub hlwb txuas ntxiv
Cov nyhuv neuroproTective ntawm Udca stems los ntawm nws cov kev cai ntawm cov kua txiv qaub teeb liab txoj kev teeb tsa, mitochondrial muaj nuj nqi, thiab neuroinflamation. Cov txheej txheem no yog nyob rau hauv txoj kab nrog cov tub ntxhais ntxhais lub siab kho mob, tab sis cov ntaub so ntswg tau nthuav dav los ntawm daim siab mus rau hauv nruab nrab lub paj hlwb.
Mitochondrial tiv thaiv: sib ntaus sib tua lub zog hluav taws xob ntawm neurons
Neurons mas cia siab rau Mitochondria rau cov khoom siv hluav taws xob, thiab mitochondment ua haujlwm yog cov kab mob tseem ceeb ntawm cov kab mob Alzheimer xws li Alzheimer tus kab mob (Ad) thiab tus kab mob Parkinson (PD). UDCA txhim kho mitochondrial muaj nuj nqi los ntawm txoj kev hauv qab no:
Stabilizing membrane muaj peev xwm:Udca tuaj yeem ntxig rau hauv mitochondrial membrane, xws li tswj hwm tus membropholic bile acids (kev tiv thaiv kev tso tawm ntawm cytochrome c thiab lub apoptotics cascade.
Txhawb nqa ATP Synthesis:Nyob rau hauv cov qauv kawm ntawv, UDCA (50-100 μm) tuaj yeem kho cov kev ua ntawm mitochondrial complex Kuv, nce Atp ntau lawm 30%, thiab txhim kho cov khoom siv neuronal.
Inhibit oxidating kev ntxhov siab:UDCA Upregulates cov haujlwm ntawm superoxide dismutase (sod) thiab glutathune pitochidase (GPX), txo cov oxygen hom (Ros) kev puas tsuaj oxidative.
Inhibiting Neuroinflammation: Ua txhaum txoj kev ntev ntev
Neuroinflamation yog tus tsav tsheb tseem ceeb ntawm cov kab mob neurodegenerative ntawm microglia thiab kev tso tawm}}} 1, tnf {{4 4}}). UDCA exerts anti-inflammatory cuam tshuam los ntawm cov txheej txheem nram qab no:
Kev tswj hwm micoglial cell phenotype:Hauv PD Qauv, UDCA (25 MG / KG / D, Or {}}} Txoj kev hloov pauv M2} Txoj kev hloov pauv ntawm IL-6 hauv Cerebrospinal kua los ntawm 40%.
Inhibiting nf -} κb txoj hauv kev:UDCA Blocks IκB kev txiav txim siab, txo cov kev sib tsoo nuclear ntawm nf {{} {} {κ} κ κ κ κ {{oks} pob txha. Nyob rau hauv AD nas qauv, UDCA kev kho mob txo qis nf {{}}}}}}}}}}}}}}}}}}% redမuronal poob los ntawm 30%.
Kev tswj hwm lub plab -}} lub hlwb axis:UDCA tuaj yeem hloov cov lej ntawm cov plab microbiota (txo cov kev nplua mais fattyoxins (xws li lps) rau hauv lub hlwb, thiab ncaj qha inhibit neuroinlammegation.
Cov pov thawj ua pov thawj: los ntawm cov tsiaj tsiaj rau cov kev siv tib neeg
Ad Qauv: Nyob rau hauv app / Ps1 Transgenic Mice, tom qab 6 lub hlis ntawm Udca (100 mg / d, intraperStendoneal txhaj tshuaj poob qis los ntawm 35%, thiab kev nthuav dav dav dav dav.
Pd qauv:Nyob rau hauv MPTP -} induced pd nas, UDCA (50 MG / D, OCL / D, Ocerary Formal Isbies los ntawm 50%.
QIB QAUV:Hauv cov nas nyob sab nraud qauv, UDCA (200 mg / kg, ib leeg intraperitonal txhaj tshuaj los ntawm 40% thiab txhim kho cov qhab nia ntawm neurological neurological neurological.
Txawm hais tias UDCA tseem tsis tau pom zoo rau kev siv nyob rau hauv cov kab mob neurological, PSCAs
Anti -}}}}}}}}}}}}}} }inginging and and and thiab Metabolic reprroegramming ntawm senterescent
Kev tsub zuj zuj ntawm cov hlwb senescent (senterescent hlwb) yog cov tseem ceeb ntawm cov nqaij mos (cov procks} UDCA cov khoom pov thawj los tiv thaiv- Kev laus}} Kev laus}}}}}}} Kev muaj peev xwm los ntawm kev xaiv xov tooj ntawm tes thiab txhim kho ntawm cov tswv yim hauv vaj tsev mentasis.
Xaiv kev tshem tawm ntawm cov hlwb Senescent: Kev sib tw Mitochondrial Pathwotic
UDCA tuaj yeem ua tau tshwj xeeb tshaj tawm kev ua yeeb yam ntawm cov hlwb senterescent thaum tsis muaj qhov cuam tshuam tseem ceeb ntawm cov hlwb ib txwm muaj. Tus txheej txheem yog cuam tshuam nrog Mitochondrial ua hauj lwm nyob rau hauv lub hlwb senterescent:
Bax / Bak ua kom: Udca (20-50 μm), txhawb nqa lub pitochondization c thiab ua kom tiav Caspase-3, thaum kawg ua rau apoptosis.
Ros - Nyob ntawm: Cov neeg muaj lub hauv paus pib yog nyob rau hauv "Oxidative Internet ua ntej ntawm Mitochondrial Ros. Udca ntxiv tsa cov qib Ros mus rau theem pib, thaum lub sij hawm lub cev tsis tuaj yeem ua siab ntev vim lawv muaj zog antioxidant muaj peev xwm.
Txhim kho cov meostasis: sorteracting kev laus {{}}}}} cov metabolic cuam tshuam
Kev laus yog ze rau metabolic syndrome (rog, cov tshuaj insulin tiv thaiv, lipid metabolism tsis sib haum). UDCA txhim kho cov metabolism los ntawm kev tswj hwm cov kua txiv qaub - fxr / tgr5 sgr5 signinging txoj kev:
Ua kom lub TGR5 receptor: Udca yog lub ntuj ligand ntawm tgr5, thiab nws txoj kev ua kom muaj peev xwm txhawb nqa cov ntaub so ntswg dawb (wat), nce hluav taws xob. Hauv cov nas laus, tom qab 8 lub lis piam ntawm kev kho nrog UDCA (0.5% W / W, Kev noj haus ntxiv rau ntawm 20% thiab insulin rhiab rhiab ntawm 30%.
Inhibiting FXR no: Hauv daim siab, UDCA kev ua haujlwm tsis zoo rau FXR, txo cov lipetion ib txwm qis - qhov lasprotein (LDL). Nyob rau hauv qhov tsis -}}}} Kev tua tsiaj rog (Nafld) qauv, UDCA tuaj yeem txo cov kev chim cov nyiaj hli los ntawm 40%.
Kev nthuav tawm lub neej noj qab haus huv: kev ua ntej siv tau hauv cov tsiaj tsiaj
Nyob rau hauv lub ntuj laus cov qauv nas, tom qab 12 lub hlis ntawm kev kho mob nrog UDCA (0.2% W / W, kev noj haus ntau ntxiv), xws li kev sib txawv ntawm kev sib ntxiv), xws li kev sib txawv ntawm kev sib ntxiv), thiab kev sib txawv ntawm cov pathology), thiab cov kab mob scleros) txo los ntawm 50%. Lub tshuab siv tau cuam tshuam nrog txo cov kev sib txuam ntawm cov hlwb senterescation, inhibiting ntev mob, thiab txhim kho cov khoom siv meabolic. Txawm hais tias tib neeg anti {{{{{{{}} Kev Tshawb Fawb Kev Nyab Xeeb (LD50 50000
Xaus: Hla - ciam teb sib tawg ntawm cov kab mob siab rau kev laus
Cov neuroprotective thiab anti -}}}}}} Cov peev txheej ntawm nws cov cim mole thiab ntau {1} {hom phiaj ua tshuab. Los ntawm Mitochondrial tiv thaiv rau inhibition ntawm neuroincrammegation, los ntawm kev tshem tawm cov kab mob sentericming los ntawm kev cuam tshuam ntawm kev cuam tshuam ntawm kev laus- cov kab mob uas muaj feem xyuam. Nyob rau yav tom ntej, nrog kev tshawb fawb txog cov kuaj mob, kev kho mob lub neej ", muab cov tswv yim zoo rau tib neeg los tawm tsam cov kab mob nurodegenerative cov kab mob thiab kev laus.
Cim npe nrov: ursodeoxychholic acid qhia li cas 128-13-2, cov neeg tsim khoom, chaw tsim khoom, Hoobkas, lag luam, yuav, ntau, loj, rau muag