ndabere

Ezetimibe bụ onye nwere ike na onye na-egbochi nnabata cholesterol [1].

Cholesterol bụ molekul lipid na achọrọ iji wulite ma jikwaa nguzozi n'usoro nke membranes na mmiri. Ọzọkwa, ọ na-eje ozi dị ka precursor nke vitamin D, bile acids na steroid homonụ.

N'ime mkpụrụ ndụ Caco-2 dị iche iche etinyere ya na carotenoid (1 μM), ezetimibe (10 mg / L) gbochiri ụgbọ njem carotenoid na mgbochi 50% maka ɑ-carotene na β-carotene. Ọzọkwa, ọ gbochiri ibufe β-cryptoxanthin, lycopene na lutein: zeaxanthin (1:1). N'otu oge ahụ, ezetimibe gbochiri mbufe cholesterol site na 31%. Ezetimibe belatara okwu nke ndị na-anabata elu SR-BI, onye na-ebugharị kasetị ATP, subfamily A (ABCA1), Niemann-Pick ụdị C1 Dị ka protein 1 (NPC1L1) na retinoid acid receptor (RAR) γ, sterol-regulatory element na-ejikọta protein SREBP -1 na SREBP-2, na imeju X receptor (LXR) β [3].

N'ime apolipoprotein E knockout (apoE-/-) ụmụ oke, ezetimibe (3 mg / kg) gbochiri nnabata cholesterol site na 90%. Ezetimibe belatara cholesterol plasma, mmụba HDL, ma gbochie ọganihu nke atherosclerosis [1]. N'ime ule nke atọ nke mmadụ, Ezetimibe (10 mg) belatara nke ukwuu ọkwa LDL cholesterol, mkpokọta cholesterol na triglycerides wee mụbaa ọkwa HDL cholesterol [2].

Ntụaka:
[1]. Davis HR Jr, Compton DS, Hoos L, et al. Ezetimibe, onye na-egbochi nnabata cholesterol dị ike, na-egbochi mmepe nke atherosclerosis na ụmụ oke ApoE knockout. Arterioscler Thromb Vasc Biol, 2001, 21 (12): 2032-2038.
[2]. Clader JW. Nchọpụta ezetimibe: echiche sitere na mpụga onye na-anabata ya. J Med Chem, 2004, 47 (1): 1-9.
[3]. N'oge A, Dawson HD, Harrison EH. A na-ebelata ụgbọ njem carotenoid na ngosipụta nke ndị na-ebu lipid SR-BI, NPC1L1 na ABCA1 na-agbadata na sel Caco-2 nke ezetimibe na-emeso ya. J Nutr, 2005, 135 (10): 2305-2312.

Nkọwa

Ezetimibe (SCH 58235) bụ onye na-egbochi nnabata cholesterol dị ike. Ezetimibe bụ ihe mgbochi Niemann-Pick C1-like1 (NPC1L1), ma bụrụ onye na-eme Nrf2 ike.

Na Vitro

Ezetimibe (Eze) na-arụ ọrụ dị ka onye na-arụ ọrụ Nrf2 dị ike n'emeghị ka cytotoxicity. Ezetimibe na-akwalite transactivation nke Nrf2, dị ka onye nta akụkọ luciferase gosipụtara. Ezetimibe na-akwalitekwa mkpụrụ ndụ ihe nketa Nrf2, gụnyere GSTA1, heme oxygenase-1 (HO-1) na Nqo-1 na sel Hepa1c1c7 na MEF. Ezetimibe na-edozi mkpụrụ ndụ ihe mgbaru ọsọ Nrf2 na sel Nrf2 +/+ MEF, ebe a na-egbochi ntinye a na Nrf2-/- MEF sel. N'ịchịkọta ọnụ, Ezetimibe na-arụ ọrụ dị ka akwụkwọ akụkọ Nrf2 inducer n'ụzọ na-adabereghị na ROS[1]. A na-eji Ezetimibe agwọ ọrịa hepatocytes mmadụ huh7 (10μM, 1 h) ma tinye ya na palmitic acid (PA, 0.5 mM, 24 h) iji kpalite steatosis imeju. Ọgwụ Ezetimibe na-ebelata ọkwa PA-abawanye triglycerides (TG), nke dabara na ọmụmụ anụmanụ anyị. Ọgwụgwọ PA rụpụtara ihe dị ka 20% mRNA okwu ATG5, ATG6, na ATG7, nke ọgwụgwọ Ezetimibe mụbara. Na mgbakwunye, ọgwụgwọ Ezetimibe mụbara nke ukwuu mbelata nke PA na-akpata na ụba protein LC3[2].

MCE akwadobeghị izi ezi nke ụzọ ndị a. Ha bụ naanị maka ntụnye aka.

Nlekọta Ezetimibe (Eze) na-ebelata ibu imeju ụmụ oke na-eri nri methionine na choline deficient (MCD). Nke a dabara na mmetụta bara uru nke Ezetimibe na steatosis imeju. Akụkọ ihe mere eme imeju na-egosi na a na-akpọ ọtụtụ ụmụ irighiri abụba macrovesicular na ụmụ oke na nri MCD, mana ọgwụgwọ Ezetimibe na-ebelata nke ọma ọnụ ọgụgụ na nha nke ụmụ irighiri mmiri ndị ahụ. Ọzọkwa, fibrosis imeju na ụmụ oke na-enye nri MCD bụ nke Ezetimibe[1] na-ebelata nke ukwuu. Ọbara na lipid ọkwa imeju gụnyere TG, free fatty acids (FFA), na mkpokọta cholesterol (TC) na-ebelata nke ukwuu na oke OLETF na-agwọ Ezetimibe. Ọzọkwa, oke OLETF na-egosi ọkwa dị elu nke glucose, insulin, HOMA-IR, TG, FFA, na TC karịa anụmanụ LETF, nke Ezetimibe belatara nke ukwuu. Na mgbakwunye, nyocha akụkọ ihe mere eme gosiri na oke nchịkwa OLETF gosipụtara ụmụ irighiri mmiri dị ukwuu na hepatocytes karịa njikwa LETO dabara na afọ, nke nchịkwa Ezetimibe[2 na-ebelata].

Nchekwa

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