Effects of telmisartan on the expression of matrix metalloproteinase-13 and its tissue inhibitor-1 and insulin resistance in nonalcoholic steatohepatitis rat model

Abstract

Objective To study the effects of telmisartan on matrix metalloproteinase-13(MMP-13) and tissue inhibitor of metallo- proteinase-1(TIMP-1) expressions and insulin resistance in rat model of nonalcoholic steatohepatitis(NASH).Methods Thirty male SD rats were randomized into normal control group,NASH model group and telmisartan intervention group.The rats were given standard food in normal control group,while high fat diet for 16 weeks in the other two groups to induce NASH.In telmisartan intervention group, telmisartan[5 mg/(kg·d)]was adminstrated intragastrically for 4 weeks since the 12th week.All animals were sacrificed at 16 weeks. Serum levels of alanine aminotransferase(ALT),aspartate transaminase(AST),fasting blood glucose(FBG) and fasting insulin(FINS) were detected.Insulin sensitivity was evaluated by homeostasis model assessment of insulin resistance(HOMA-IR).Western blot and RT-PCR were used to measure TIMP-1 and MMP-13 expressions in hepatic tissue.Histological observation and immunohistochemical staining ofα-smooth muscle actin(α-SMA) were also performed.Results Serum levels of ALT,AST,FPG,FINS and HOMA-IR were significantly higher in NASH group than in normal control group(P0.01).Compared with NASH group,serum levels of ALT,FPG, FINS and HOMA-IR decreased significantly(P0.01),and AST level also decreased,but with no significance(P0.05).Telmisartan improved significantly hepatic inflammation and fibrosis(P0.01),decreased HOMA-IR significantly(P0.01),reduced expresseions ofα-SMA and TIMP-1,and increased expressions of MMP-13 in hepatic tissue(P0.01).Conclusion Telmisartan can improve insulin resistance and prevent hepatic fibrosis in NASH rats.