title: Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes.
abstract: 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 α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) 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 α-SMA, TGF-β1, TNF-α 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 α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Guifen
authors.initials: G
authors.lastname: Qiang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiuying
authors.initials: X
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xuan
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.forename: Hengai
authors.initials: H
authors.lastname: Zhang
authors.forename: Bainian
authors.initials: B
authors.lastname: Chen
authors.forename: Xiaoxiu
authors.initials: X
authors.lastname: Li
authors.forename: Mian
authors.initials: M
authors.lastname: Zu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Haiguang
authors.initials: H
authors.lastname: Yang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine