Hussien Noha I, El-Kerdasy Hanan I, Ibrahim Mohammad El-Tantawy
a Department of Physiology, Faculty of Medicine, Benha University, Egypt.
b Department of Anatomy, Faculty of Medicine, Benha University, Egypt.
Can J Physiol Pharmacol. 2017 Dec;95(12):1433-1441. doi: 10.1139/cjpp-2017-0070. Epub 2017 Jul 31.
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.
非酒精性脂肪性肝病（NAFLD）是肝脏发病和死亡的主要原因，目前仍没有经证实有效的治疗方法。内源性大麻素系统在各种肝脏疾病中发挥重要作用。激活素A是转化生长因子β（TGF-β）超家族的成员，可抑制肝细胞生长。卵泡抑素可拮抗激活素A的生物学作用。本研究旨在探讨利莫那班（一种有效的大麻素受体1（CB1）拮抗剂）对胆碱缺乏（CD）饮食诱导的大鼠NAFLD的影响，并检测其是否能改变肝脏中激活素A和卵泡抑素的表达。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（由CD饮食诱导的NAFLD）；以及CD饮食+利莫那班组（用利莫那班治疗的NAFLD）。结果发现，CD饮食导致肝脏指数、血清肝酶水平、丙二醛（MDA）、TGF-β1、激活素A以及肝组织中CB1表达显著增加，而肝脏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。与仅喂食CD饮食的组相比，给予利莫那班显著改善了所有研究参数。组织病理学检查支持了这些结果。我们得出结论，利莫那班通过降低氧化应激和TGF-β1的肝脏表达，并调节激活素A和卵泡抑素的肝脏表达，显著对抗了CD饮食诱导的NAFLD。
