Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes

被引：51

作者：

Qiang, Guifen ^{[2
,3
]}

Zhang, Li ^{[2
,4
]}

Yang, Xiuying ^{[2
,4
]}

Xuan, Qi ^{[5
]}

Shi, Lili ^{[2
]}

Zhang, Hengai ^{[2
]}

Chen, Bainian ^{[2
]}

Li, Xiaoxiu ^{[2
]}

Zu, Mian ^{[2
,4
]}

Zhou, Dan ^{[2
,4
]}

Guo, Jing ^{[2
,4
]}

Yang, Haiguang ^{[2
,4
]}

Du, Guanhua ^{[1
,2
,4
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, Natl Ctr Pharmaceut Screening, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Aerosp Ctr Hosp, Beijing 100049, Peoples R China

[4] Beijing Key Lab Drug Target Identificat & Drug Sc, Beijing 100050, Peoples R China

[5] Capital Med Univ, Xuanwu Hosp, Beijing 100053, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2012年 / 685卷 / 1-3期

基金：

中国国家自然科学基金;

关键词：

Valsartan; Type; 2; diabetes; Hepatic fibrosis; Pathological progression; Nonalcoholic fatty liver disease; FATTY LIVER-DISEASE; TRANSFORMING GROWTH FACTOR-BETA-1; ANGIOTENSIN-II; STELLATE CELLS; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; RECEPTOR ANTAGONIST; GENE-EXPRESSION; PROLIFERATION; STEATOSIS;

D O I：

10.1016/j.ejphar.2012.04.028

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of alpha-smooth-muscle-actin (alpha-SMA), transforming growth factor beta 1 (TGF-beta 1), tumor necrosis factor (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of alpha-SMA, TGF-beta 1, TNF-alpha and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing alpha-SMA, TGF-beta 1, TNF-alpha and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

引用

页码：156 / 164

页数：9

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