Protective effect of rimonabant, a canabinoid receptor 1 antagonist, on nonalcoholic fatty liver disease in a rat model through modulation of the hepatic expression of activin A and follistatin.
Protective effect of rimonabant, a canabinoid receptor 1 antagonist, on nonalcoholic fatty liver disease in a rat model through modulation of the hepatic expression of activin A and follistatin.
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利莫那班（一种大麻素受体 1 拮抗剂）通过调节激活素 A 和卵泡抑素的肝脏表达对大鼠模型中的非酒精性脂肪肝具有保护作用。
DOI：
10.1139/cjpp-2017-0070
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发表时间：
2017
影响因子：
2.1
通讯作者：
Mohammad Ibrahim
中科院分区：
文献类型：
--
作者：
Noha I Hussien;Hanan I. El;Mohammad Ibrahim
非酒精性脂肪性肝病（NAFLD）是肝脏发病率和死亡率的主要原因，目前仍没有有效的治疗方法。内源性大麻素系统在各种肝脏疾病中发挥着重要作用。激活素A是转化生长因子β（TGF-β）超家族的成员，并抑制肝细胞生长。卵泡抑素拮抗激活素A的生物学作用。本研究旨在研究利莫那班（一种有效的大麻素受体1（CB 1）拮抗剂）对胆碱缺乏（CD）饮食诱导的大鼠NAFLD的影响，以及检测它是否可以改变激活素A和卵泡抑素的肝脏表达。将40只大鼠分为4组：对照组、利莫那班治疗组（接受利莫那班的正常大鼠）、CD饮食组（用CD饮食诱导的NAFLD）和CD饮食+利莫那班组（用利莫那班治疗的NAFLD）。结果表明，CD组大鼠肝指数、血清肝酶水平、肝组织中丙二醛（MDA）、TGF-β1、激活素A和CB 1表达显著升高，肝组织中谷胱甘肽过氧化物酶（GSH-Px）和卵泡抑素mRNA表达显著降低。与单独喂食CD饮食的组相比，给予利莫那班显著改善了所有研究参数。组织学检查支持这些结果。我们的结论是，利莫那班通过降低氧化应激和肝脏TGF-β1的表达，以及调节肝脏激活素A和卵泡抑素的表达，显著抵消了CD饮食诱导的NAFLD。
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin. Forty rats were distributed among 4 groups: the control group, the rimonabant treatment group (normal rats that received rimonabant); the CD diet group (NAFLD induced with a CD diet); and the CD diet + rimonabant group (NAFLD treated with rimonabant). It was found that the CD diet caused significant increase in liver index, serum levels of liver enzymes, malondialdehyde (MDA), TGF-β1, activin A, and CB1 expression in liver tissue, with a significant decrease in glutathione peroxidase (GSH-Px) and follistatin mRNA expression in liver tissues. The administration of rimonabant significantly improved all of the studied parameters compared with the group fed the CD diet alone. Histopathological examination supported these results. We concluded that rimonabant significantly counteracted NAFLD induced with the CD diet by decreasing oxidative stress and hepatic expression of TGF-β1, and modulating the hepatic expression of activin A and follistatin.
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影响因子：
6.6
作者：
Gornicka, Agnieszka;Morris-Stiff, Gareth;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
影响因子：
25.7
作者：
Malhi, Harmeet;Kaufman, Randal J.
通讯作者：
Kaufman, Randal J.
影响因子：
29
作者：
Tam J;Cinar R;Liu J;Godlewski G;Wesley D;Jourdan T;Szanda G;Mukhopadhyay B;Chedester L;Liow JS;Innis RB;Cheng K;Rice KC;Deschamps JR;Chorvat RJ;McElroy JF;Kunos G
通讯作者：
Kunos G
影响因子：
15.9
作者：
Osei-Hyiaman, Douglas;Liu, Jie;Kunos, George
通讯作者：
Kunos, George