Abstract: Objective To determine whether RhoA/Rho-kinase is involved in the pathogenesis of hepatic fibrosis in rats with type 2 diabetes. Methods An animal model of type 2 diabetes was developed by high fat diet combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30mg/kg, i.p.). Fasting blood glucose, triglycerides, cholesterol, aspartate aminotransferase and alanine aminotransferase was measured. The deposition of collagen in liver was evaluated by Masson staining and the hydroxyproline determination. The mRNA expressions of transforming growth factor (TGF-β1) and connective tissue growth factor (CTGF) in liver tissue were assessed by RT-PCR. Immunohistochemistry staining for TGF-β1 was performed. The phosphorylation of myosin phosphatase target subunit 1(p-MYPT1) was measured by Western blot analysis. Results Compared with control rats, Blood glucose, blood fat, aminotransferase and the deposition of collagen in the liver in the untreated diabetic rats was significantly increased (P＜0.01); p-MYPT1 and TGF-β1 protein, the mRNA expression of TGF-β1 and CTGF was significantly enhanced (P＜0.01). Compared with untreated diabetic rats, treatment with fasudil significantly decreased aminotransferase, deposition of collagen, p-MYPT1, mRNA expression of TGF-β1 and CTGF (P＜0.01). Conclusions Hyperglycemia can activate the RhoA/Rho-kinase which maybe regulates TGF-β1/CTGF expression in liver tissues. RhoA/Rho-kinase plays an importent role in the development of diabetic liver fibrosis.

Key words: diabetic liver fibrosis, Rho-kinase, transforming growth factor beta 1, connective tissue growth factor, fasudil