abẹlẹ

Ezetimibe jẹ apaniyan ti o lagbara ati aramada ti gbigba idaabobo awọ [1].

Cholesterol jẹ moleku ọra ati pe o nilo lati kọ ati ṣetọju iduroṣinṣin igbekalẹ membran ati ito.Paapaa, o ṣiṣẹ bi iṣaaju ti Vitamin D, awọn acid bile ati awọn homonu sitẹriọdu.

Ninu awọn sẹẹli Caco-2 ti o ni iyatọ ti o wa pẹlu carotenoid (1 μM), ezetimibe (10 mg / L) ti ṣe idiwọ gbigbe ọkọ carotenoid pẹlu 50% idinamọ fun ɑ-carotene ati β-carotene.Pẹlupẹlu, o ṣe idiwọ gbigbe ti β-cryptoxanthin, lycopene ati lutein: zeaxanthin (1: 1).Ni akoko kanna, ezetimibe ṣe idiwọ gbigbe idaabobo awọ nipasẹ 31%.Ezetimibe dinku ikosile ti awọn olugba dada SR-BI, ATP abuda kasẹti gbigbe, subfamily A (ABCA1), Niemann-Pick iru C1 Like 1 protein (NPC1L1) ati retinoid acid receptor (RAR) γ, sterol-ilana ano abuda awọn ọlọjẹ SREBP -1 ati SREBP-2, ati ẹdọ X olugba (LXR) β [3].

Ni apolipoprotein E knockout (apoE-/-) eku, ezetimibe (3 mg/kg) ṣe idiwọ gbigba idaabobo awọ nipasẹ 90%.Ezetimibe dinku idaabobo awọ pilasima, awọn ipele HDL pọ si, o si ṣe idiwọ ilọsiwaju ti atherosclerosis [1].Ni ipele III awọn idanwo eniyan, Ezetimibe (10 miligiramu) dinku ni pataki awọn ipele LDL idaabobo awọ, idaabobo awọ lapapọ ati triglycerides ati alekun ipele ti HDL cholesterol [2].

Awọn itọkasi:
[1].Davis HR Jr, Compton DS, Hoos L, et al.Ezetimibe, oludena gbigba idaabobo awọ ti o lagbara, ṣe idiwọ idagbasoke ti atherosclerosis ni awọn eku ApoE knockout.Arterioscler Thromb Vasc Biol, 2001, 21 (12): 2032-2038.
[2].Clader JW.Awari ti ezetimibe: wiwo lati ita olugba.J Med Chem, 2004, 47 (1): 1-9.
[3].Lakoko A, Dawson HD, Harrison EH.Gbigbe Carotenoid dinku ati ikosile ti awọn olutọpa ọra SR-BI, NPC1L1, ati ABCA1 ti wa ni isalẹ ni awọn sẹẹli Caco-2 ti a tọju pẹlu ezetimibe.J Nutr, 2005, 135 (10): 2305-2312.

Apejuwe

Ezetimibe (SCH 58235) jẹ oludena gbigba idaabobo awọ to lagbara.Ezetimibe jẹ oludaniloju Niemann-Pick C1-like1 (NPC1L1), ati pe o jẹ oluṣe Nrf2 ti o lagbara.

Ninu Vitro

Ezetimibe (Eze) n ṣiṣẹ bi oluṣe Nrf2 ti o lagbara lai fa cytotoxicity.Ezetimibe ṣe ilọsiwaju iṣowo ti Nrf2, bi a ti fi han nipasẹ aṣeyẹwo onirohin luciferase.Ezetimibe tun ṣe atunṣe awọn Jiini afojusun Nrf2, pẹlu GSTA1, heme oxygenase-1 (HO-1) ati Nqo-1 ni Hepa1c1c7 ati awọn sẹẹli MEF.Ezetimibe ṣe atunṣe awọn Jiini ibi-afẹde Nrf2 ni awọn sẹẹli Nrf2 +/+ MEF, lakoko ti ifilọlẹ yii ti dina patapata ni awọn sẹẹli Nrf2-/- MEF.Papọ, Ezetimibe ṣe bi aramada Nrf2 inducer ni ọna ominira ROS[1].Human huh7 hepatocytes ti wa ni itọju pẹlu Ezetimibe (10μM, 1 h) ati idawọle pẹlu palmitic acid (PA, 0.5 mM, 24 h) lati fa steatosis ẹdọforo.Itọju Ezetimibe ni pataki ṣe idinku awọn ipele triglycerides (TG) ti PA ti o pọ si, eyiti o ni ibamu pẹlu ikẹkọ ẹranko wa.Itọju PA jẹ abajade isunmọ 20% idinku ninu ikosile mRNA ti ATG5, ATG6, ati ATG7, eyiti o ti pọ si nipasẹ itọju Ezetimibe.Ni afikun, itọju Ezetimibe ni pataki pọ si idinku ti o fa PA ni ọpọlọpọ amuaradagba LC3[2].

MCE ko tii jẹrisi deede awọn ọna wọnyi.Wọn wa fun itọkasi nikan.

Isakoso ti Ezetimibe (Eze) dinku awọn iwuwo ẹdọ ti awọn eku ti a jẹ ounjẹ methionine- ati choline-deficient (MCD).Eyi ni ibamu pẹlu awọn ipa anfani ti Ezetimibe lori steatosis ẹdọ.Itan-akọọlẹ ẹdọ fihan awọn isunmi ọra marovesikula pupọ ninu awọn eku lori ounjẹ MCD, ṣugbọn itọju Ezetimibe ni pataki dinku nọmba ati iwọn awọn isunmi wọnyẹn.Pẹlupẹlu, fibrosis ẹdọ ninu awọn eku ti o jẹun ni ounjẹ MCD jẹ idinku ni pataki nipasẹ Ezetimibe[1].Ẹjẹ ati awọn ipele ọra ẹdọ pẹlu TG, ọra acids ọfẹ (FFA), ati idaabobo awọ lapapọ (TC) dinku ni pataki ni awọn eku OLETF ti Ezetimibe ṣe itọju.Pẹlupẹlu, awọn eku OLETF ṣe afihan awọn ipele omi ara ti o ga julọ ti glukosi, insulin, HOMA-IR, TG, FFA, ati TC ju awọn ẹranko LETF lọ, eyiti Ezetimibe dinku ni pataki.Ni afikun, itupalẹ itan-akọọlẹ fihan pe awọn eku iṣakoso OLETF ṣe afihan awọn isunmi lipid ti o tobi ni hepatocytes ju awọn iṣakoso LETO ti ọjọ-ori lọ, eyiti o jẹ idinku nipasẹ iṣakoso Ezetimibe[2].

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