Zhang Wei, Xu Yi-Zhi, Liu Bo, Wu Rong, Yang Ying-Ying, Xiao Xiao-Qiu, Zhang Xia
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
Department of Hematology and Oncology, Chongqing the Third Hospital, Chongqing 400014, China.
ScientificWorldJournal. 2014 Jan 14;2014:603409. doi: 10.1155/2014/603409. eCollection 2014.
Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats.
Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression.
ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group.
Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.
噻唑烷二酮类药物（TZDs）可改善非酒精性脂肪性肝炎（NASH）中的肝脂肪变性。肾素-血管紧张素系统（RAS）的主要效应物血管紧张素（Ang）II在NASH的发生和发展中起重要作用。并且一些AngII介导的效应可由TZDs调节。血管紧张素转换酶（ACE）2是RAS的一个新组分，可降解Ang II以减弱其后续的生理作用。我们旨在评估TZDs对NASH大鼠胰岛素敏感组织中ACE2表达的影响。
40只大鼠分为正常对照组、高脂饮食（HFD）组、吡格列酮对照组和HFD加吡格列酮组。治疗24周后，我们评估了肝脏组织学和组织特异性ACE2表达的变化。
与正常对照组相比，HFD组肝脏和脂肪组织中ACE2基因和蛋白表达显著更高，而在骨骼肌中显著降低。与HFD组相比，吡格列酮显著降低了肝脂肪变性程度。与HFD组相比，吡格列酮显著增加了肝脏、脂肪组织和骨骼肌中ACE2蛋白表达。
吡格列酮改善了高脂饮食诱导的NASH大鼠的肝脂肪变性，并上调了胰岛素敏感组织中ACE2的表达。
