Imvelaphi

I-Ezetimibe inamandla kwaye inoveli inhibitor yokufunxa i-cholesterol [1].

I-cholesterol yi-lipid molekyuli kwaye iyafuneka ukuze kwakhiwe kwaye kugcinwe i-membrane ingqibelelo yesakhiwo kunye nolwelo. Kwakhona, isebenza njenge-precursor ye-vitamin D, i-bile acids kunye neehomoni ze-steroid.

Kwiiseli ezihlukeneyo zeCaco-2 ezifakwe kwi-carotenoid (1 μM), ezetimibe (10 mg / L) inqanda ukuthuthwa kwe-carotenoid kunye ne-50% inhibition ye-ɑ-carotene kunye ne-β-carotene. Kwakhona, yayinqanda ukuthuthwa kwe-β-cryptoxanthin, i-lycopene kunye ne-lutein: zeaxanthin (1: 1). Kwangaxeshanye, ezetimibe inqanda ukuthuthwa kwe-cholesterol ngama-31%. I-Ezetimibe iyancipha ukubonakaliswa kwe-surface receptors SR-BI, i-ATP ebophelelayo isithuthi sekhasethi, i-subfamily A (ABCA1), i-Niemann-Pick uhlobo lwe-C1 Njenge-protein ye-1 (NPC1L1) kunye ne-retinoid acid receptor (RAR) γ, i-sterol-regulatory element ebopha iiprotheni SREBP -1 kunye ne-SREBP-2, kunye ne-X receptor yesibindi (LXR)β [3].

Kwi-apolipoprotein E knockout (apoE-/-) iigundane, ezetimibe (3 mg/kg) inqanda ukufunxwa kwe-cholesterol ngama-90%. I-Ezetimibe inciphisa i-cholesterol ye-plasma, yandisa amanqanaba e-HDL, kwaye inqanda ukuqhubeka kwe-atherosclerosis [1]. Kwinqanaba le-III izilingo zabantu, i-Ezetimibe (10 mg) yanciphisa kakhulu amanqanaba e-cholesterol ye-LDL, i-cholesterol epheleleyo kunye ne-triglycerides kwaye yandisa izinga le-HDL cholesterol [2].

IiReferensi:
[1]. UDavis HR Jr, Compton DS, Hoos L, et al. I-Ezetimibe, i-cholesterol absorption inhibitor enamandla, inqanda ukukhula kwe-atherosclerosis kwiimpuku ze-ApoE knockout. I-Arterioscler Thromb Vasc Biol, i-2001, i-21 (12): 2032-2038.
[2]. Clader JW. Ukufunyanwa kwe-ezetimibe: umbono ovela ngaphandle kwe-receptor. J Med Chem, 2004, 47(1): 1-9.
[3]. Ngexesha A, Dawson HD, Harrison EH. Ukuthuthwa kwe-Carotenoid kuyancipha kwaye ibonakaliso ye-lipid transporters SR-BI, NPC1L1, kunye ne-ABCA1 iyancipha kwiiseli zeCaco-2 eziphathwa nge-ezetimibe. J Nutr, 2005, 135 (10): 2305-2312.

Inkcazo

I-Ezetimibe (SCH 58235) yi-cholesterol enamandla yokufunxa inhibitor. I-Ezetimibe yi-Niemann-Pick C1-like1 (NPC1L1) inhibitor, kwaye iyi-activator ye-Nrf2 enamandla.

I-In vitro

I-Ezetimibe (Eze) isebenza njenge-activator ye-Nrf2 enamandla ngaphandle kokubangela i-cytotoxicity. I-Ezetimibe iphucula ukusebenza kwe-Nrf2, njengoko ityhilwe luciferase intatheli yovavanyo. I-Ezetimibe iphinda ilawule i-Nrf2 ye-target genes, kuquka i-GSTA1, i-heme oxygenase-1 (HO-1) kunye ne-Nqo-1 kwi-Hepa1c1c7 kunye neeseli ze-MEF. I-Ezetimibe ilawula ijene ekujoliswe kuyo ye-Nrf2 kwiiseli ze-Nrf2+/+ ze-MEF, kanti oku kufakwa kuvalwe ngokupheleleyo kwiiseli ze-Nrf2-/- MEF. Ithatyathwe kunye, i-Ezetimibe isebenza njengenoveli i-Nrf2 inducer ngendlela ezimeleyo ye-ROS[1]. I-hepatocytes yabantu i-huh7 ifakwe kwangaphambili nge-Ezetimibe (10μM, 1 h) kunye ne-incubated nge-palmitic acid (PA, 0.5 mM, 24 h) ukubangela i-hepatic steatosis. Unyango lwe-Ezetimibe lunciphisa kakhulu amanqanaba e-PA-i-triglycerides (TG), ehambelanayo nesifundo sethu sezilwanyana. Unyango lwe-PA lubangele ukuhla okumalunga ne-20% kwi-mRNA expression ye-ATG5, ATG6, kunye ne-ATG7, eyonyuswe ngonyango lwe-Ezetimibe. Ukongeza, unyango lwe-Ezetimibe lwandise kakhulu ukucutha okubangelwa yi-PA kwi-LC3 yobuninzi beprotheyini [2].

I-MCE ayizange iqinisekise ngokuzimeleyo ukuchaneka kwezi ndlela. Zenzelwe ireferensi kuphela.

Ulawulo lwe-Ezetimibe (Eze) lunciphisa ubunzima besibindi beempuku ezondla i-methionine- kunye ne-choline-deficient (MCD) yokutya. Oku kuhambelana neziphumo eziluncedo ze-Ezetimibe kwi-hepatic steatosis. I-histology yesibindi ibonisa amathontsi atyebileyo e-macrovesicular amaninzi kwiimpuku kukutya kwe-MCD, kodwa unyango lwe-Ezetimibe lunciphisa ngokuphawulekayo inani kunye nobukhulu baloo mathontsi. Ngaphaya koko, i-hepatic fibrosis kwiimpuku ezondla ukutya kwe-MCD ithotywa kakhulu ngu-Ezetimibe[1]. Amanqanaba egazi kunye nesibindi se-lipid kuquka i-TG, i-fatty acids yamahhala (FFA), kunye ne-cholesterol epheleleyo (TC) iyancipha kakhulu kwiigundane ze-OLETF eziphathwa nge-Ezetimibe. Ngaphezu koko, iigundane ze-OLETF zibonisa amanqanaba aphezulu e-serum ye-glucose, i-insulin, i-HOMA-IR, i-TG, i-FFA, kunye ne-TC kunezilwanyana ze-LETF, ezincitshiswe kakhulu yi-Ezetimibe. Ukongeza, uhlalutyo lwe-histological lubonise ukuba iigundane zokulawula i-OLETF zibonise amathontsi amakhulu e-lipid kwi-hepatocytes kunolawulo lwe-LETO oluhambelana neminyaka, oluthotywayo lulawulo lwe-Ezetimibe[2].

Ugcino

Ubume beMichiza