Amavu n'amavuko

Ezetimibe ni ikintu gikomeye kandi kibuza kwanduza cholesterol [1].

Cholesterol ni molekile ya lipide kandi irasabwa kubaka no kubungabunga ibibumbano byubaka kandi bitemba.Kandi, ikora nkibibanziriza vitamine D, aside aside na hormone steroid.

Muri selile zitandukanye za Caco-2 zashyizwemo karotenoide (1 μM), ezetimibe (10 mg / L) yabujije gutwara karotenoide hamwe na 50% yabujije ɑ-karotene na β-karotene.Nanone, yabujije gutwara β-cryptoxanthin, lycopene na lutein: zeaxanthin (1: 1).Muri icyo gihe, ezetimibe yabujije gutwara cholesterol kuri 31%.Ezetimibe yagabanije imvugo yubuso bwa SR-BI, ATP ihuza cassette itwara abantu, mu buryo butemewe A (ABCA1), Ubwoko bwa Niemann-Pick Ubwoko bwa C1 Nka poroteyine 1 (NPC1L1) hamwe na reseptor acide retinoide (RAR) γ, sterol-igenga poroteyine SREBP -1 na SREBP-2, hamwe n'umwijima X wakira (LXR) β [3].

Muri apolipoprotein E knockout (apoE - / -) imbeba, ezetimibe (3 mg / kg) yabujije cholesterol kwinjiza 90%.Ezetimibe yagabanije cholesterol ya plasma, yongera urwego rwa HDL, kandi ibuza iterambere rya ateriyose [1].Mu cyiciro cya gatatu cyibigeragezo byabantu, Ezetimibe (mg 10) yagabanije cyane urugero rwa cholesterol ya LDL, cholesterol yose hamwe na triglyceride kandi byongera urugero rwa cholesterol ya HDL [2].

Reba:
[1].Davis HR Jr, Compton DS, Hoos L, nibindi.Ezetimibe, inhibitori ya cholesterol ikomeye, ibuza iterambere rya aterosklerose mu mbeba za ApoE knockout.Arterioscler Thromb Vasc Biol, 2001, 21 (12): 2032-2038.
[2].Clader JW.Ivumburwa rya ezetimibe: kureba hanze ya reseptor.J Med Chem, 2004, 47 (1): 1-9.
[3].Mugihe cya A, Dawson HD, Harrison EH.Ubwikorezi bwa Carotenoid bwaragabanutse kandi imvugo yabatwara lipide SR-BI, NPC1L1, na ABCA1 ntigabanywa muri selile Caco-2 ivurwa na ezetimibe.J Nutr, 2005, 135 (10): 2305-2312.

Ibisobanuro

Ezetimibe (SCH 58235) ni inhibitori ya cholesterol ikomeye.Ezetimibe ni Niemann-Pick C1-nka1 (NPC1L1) inhibitor, kandi ni Nrf2 ikora cyane.

Muri Vitro

Ezetimibe (Eze) ikora nka Nrf2 ikora cyane idateye cytotoxicity.Ezetimibe yongera transactivation ya Nrf2, nkuko byagaragajwe numunyamakuru wa luciferase.Ezetimibe kandi igenzura ingirabuzimafatizo za Nrf2, zirimo GSTA1, heme ogisijene-1 (HO-1) na Nqo-1 muri selile Hepa1c1c7 na MEF.Ezetimibe igenga genes ya Nrf2 muri selile ya Nrf2 + / + MEF, mugihe iyi induction ihagaritswe rwose muri selile Nrf2 - / - MEF.Ufatiye hamwe, Ezetimibe akora nk'igitabo Nrf2 inducer muburyo bwigenga bwa ROS [1].Umuntu huh7 hepatocytes yateguwe na Ezetimibe (10μM, 1 h) hamwe na acide palmitike (PA, 0.5 mM, 24 h) kugirango itere umwijima.Ubuvuzi bwa Ezetimibe butuma PA yiyongera cyane kuri triglyceride (TG), ibyo bikaba bihuye nubushakashatsi bwinyamaswa.Ubuvuzi bwa PA bwatumye hafi ya 20% igabanuka rya mRNA imvugo ya ATG5, ATG6, na ATG7, yariyongereye no kuvura Ezetimibe.Byongeye kandi, kuvura Ezetimibe byongereye cyane kugabanuka kwa PA kugabanuka kwa poroteyine ya LC3 [2].

MCE ntabwo yemeje ubwigenge ubu buryo.Nibisobanuro gusa.

Ubuyobozi bwa Ezetimibe (Eze) bugabanya uburemere bwumwijima bwimbeba zagaburiwe indyo ya methionine- na choline ibura (MCD).Ibi bihuye ningaruka nziza za Ezetimibe kuri hepatike ya hepatike.Umwijima w’umwijima werekana ibinure byinshi bya macrovesicular mu mbeba ku ndyo ya MCD, ariko kuvura Ezetimibe bigabanya cyane umubare nubunini bwibyo bitonyanga.Byongeye kandi, fibrosis ya hepatike mu mbeba yagaburiwe indyo ya MCD ihuza cyane na Ezetimibe [1].Urwego rwamaraso hamwe numwijima harimo TG, aside irike yubusa (FFA), hamwe na cholesterol yuzuye (TC) byagabanutse cyane mumbeba za OLETF zivurwa na Ezetimibe.Byongeye kandi, imbeba za OLETF zerekana serumu nyinshi ya glucose, insuline, HOMA-IR, TG, FFA, na TC kurusha inyamaswa za LETF, zigabanywa cyane na Ezetimibe.Byongeye kandi, isesengura ry’amateka ryerekanye ko imbeba zo kugenzura OLETF zerekanaga ibitonyanga binini bya lipide muri hepatocytes kuruta imyaka LETO igenzurwa n’imyaka, ibyo bikaba bihujwe n’ubuyobozi bwa Ezetimibe [2].

Ububiko

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