Ingemuva

I-Ezetimibe iyi-inhibitor enamandla futhi inoveli yokumuncwa kwe-cholesterol [1].

I-Cholesterol iyi-molecule ye-lipid futhi iyadingeka ukuze kwakhiwe futhi kugcinwe ulwelwesi ubuqotho besakhiwo kanye noketshezi.Futhi, isebenza njengesandulela se-vitamin D, i-bile acids nama-hormone e-steroid.

Kumaseli e-Caco-2 ahlukanisiwe ahlanganiswe ne-carotenoid (1 μM), ezetimibe (10 mg/L) avimbele ukuthuthwa kwe-carotenoid nge-50% yokuvimbela i-ɑ-carotene ne-β-carotene.Futhi, ivimbele ukuthuthwa kwe-β-cryptoxanthin, i-lycopene ne-lutein:zeaxanthin(1:1).Ngesikhathi esifanayo, i-ezetimibe ivimbele ukuthuthwa kwe-cholesterol ngama-31%.I-Ezetimibe yehlise ukuvezwa kwama-surface receptors i-SR-BI, i-ATP ebopha amakhasethi isithuthi, umndeni omncane A (ABCA1), i-Niemann-Pick uhlobo C1 Njengeprotheni engu-1 (NPC1L1) kanye ne-retinoid acid receptor (RAR) γ, i-sterol-regulatory element ebopha amaprotheni SREBP -1 kanye ne-SREBP-2, kanye ne-X receptor yesibindi (LXR)β [3].

Ku-apolipoprotein E knockout (apoE-/-) amagundane, ezetimibe (3 mg/kg) avimbele ukumuncwa kwe-cholesterol ngo-90%.I-Ezetimibe yehlisa i-cholesterol ye-plasma, yandisa amazinga e-HDL, futhi ivimbela ukuqhubeka kwe-atherosclerosis [1].Esigabeni sesi-III sokuhlolwa kwabantu, i-Ezetimibe (10 mg) inciphise kakhulu amazinga e-cholesterol ye-LDL, i-cholesterol ephelele ne-triglycerides futhi yandisa izinga le-HDL cholesterol [2].

Izithenjwa:
[1].UDavis HR Jr, Compton DS, Hoos L, et al.I-Ezetimibe, i-cholesterol absorption inhibitor enamandla, ivimbela ukukhula kwe-atherosclerosis kumagundane e-ApoE knockout.I-Arterioscler Thromb Vasc Biol, 2001, 21(12): 2032-2038.
[2].Clader JW.Ukutholwa kwe-ezetimibe: umbono ovela ngaphandle kwesamukeli.J Med Chem, 2004, 47(1): 1-9.
[3].Ngesikhathi A, Dawson HD, Harrison EH.Ukuthuthwa kwe-carotenoid kwehlisiwe futhi ukubonakaliswa kwezithutha ze-lipid SR-BI, NPC1L1, kanye ne-ABCA1 kulawulwa phansi kumaseli e-Caco-2 aphathwa nge-ezetimibe.J Nutr, 2005, 135(10): 2305-2312.

Incazelo

I-Ezetimibe (SCH 58235) iyisivimbeli esinamandla sokumuncwa kwe-cholesterol.I-Ezetimibe iyi-Niemann-Pick C1-like1 (NPC1L1) inhibitor, futhi iyi-activator ye-Nrf2 enamandla.

Ku-Vitro

I-Ezetimibe (Eze) isebenza njengesisebenzeli esinamandla se-Nrf2 ngaphandle kokubangela i-cytotoxicity.I-Ezetimibe ithuthukisa ukusebenza kwe-Nrf2, njengoba kwembulwe i-luciferase reporter assay.I-Ezetimibe iphinde ilawule izakhi zofuzo eziqondiwe ze-Nrf2, okuhlanganisa i-GSTA1, i-heme oxygenase-1 (HO-1) ne-Nqo-1 kumaseli we-Hepa1c1c7 kanye ne-MEF.I-Ezetimibe ilawula izakhi zofuzo eziqondiwe ze-Nrf2 kumaseli e-Nrf2+/+ MEF, kuyilapho lokhu kungeniswa kuvinjwe ngokuphelele kumaseli e-Nrf2-/- MEF.Ihlanganiswe ndawonye, ​​i-Ezetimibe isebenza njengenoveli i-Nrf2 inducer ngendlela ezimele ye-ROS[1].Ama-hepatocyte angama-huh7 omuntu enziwa ngaphambili nge-Ezetimibe (10μM, 1 h) futhi ifakwe i-palmitic acid (PA, 0.5 mM, 24 h) ukuze ifake i-hepatic steatosis.Ukwelashwa kwe-Ezetimibe kuwanciphisa kakhulu amazinga e-PA-akhuphuka e-triglycerides (TG), okuhambisana nocwaningo lwethu lwezilwane.Ukwelashwa kwe-PA kuholele ekwehleni okucishe kube ngama-20% kwenkulumo ye-mRNA ye-ATG5, ATG6, ne-ATG7, ekhuphuke ngokwelashwa kwe-Ezetimibe.Ukwengeza, ukwelashwa kwe-Ezetimibe kwandisa kakhulu ukuncipha okwenziwe yi-PA ku-LC3 yobuningi bamaprotheni[2].

I-MCE ayizange iqinisekise ngokuzimela ukunemba kwalezi zindlela.Ezethenjwa kuphela.

Ukuphathwa kwe-Ezetimibe (Eze) kunciphisa isisindo sesibindi samagundane adla ukudla kwe-methionine- kanye ne-choline-deficient (MCD).Lokhu kuhambisana nemiphumela enenzuzo ye-Ezetimibe ku-hepatic steatosis.I-histology yesibindi ikhombisa ukuphinyiselwa kwamaconsi amafutha amaningi ama-macrovesicular kumagundane ekudleni kwe-MCD, kodwa ukwelashwa kwe-Ezetimibe kwehlisa inani nosayizi walawo maconsi.Ngaphezu kwalokho, i-hepatic fibrosis kumagundane adla ukudla kwe-MCD incishiswa kakhulu yi-Ezetimibe[1].Amazinga e-lipid egazi nesibindi okuhlanganisa i-TG, ama-fatty acids amahhala (FFA), kanye ne-cholesterol ephelele (TC) ehle kakhulu kumagundane e-OLETF alashwe yi-Ezetimibe.Ngaphezu kwalokho, amagundane e-OLETF abonisa amazinga aphezulu e-serum kashukela, i-insulin, i-HOMA-IR, TG, FFA, ne-TC kunezilwane ze-LETF, ezincishiswe kakhulu yi-Ezetimibe.Ngaphezu kwalokho, ukuhlaziywa kwe-histological kubonise ukuthi amagundane okulawula i-OLETF abonise amaconsi amakhulu e-lipid ku-hepatocyte kunezilawuli ze-LETO ezifaniswa neminyaka, ezincishiswa ukuphathwa kwe-Ezetimibe[2].

Isitoreji

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