Abstract
Objective: To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis. Methods: Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1. Results: After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The F values were 7.864 and 20.057 respectively. The P values were < 0.05. The differences were statistically significant. The relative expression levels of LP and OB-R mRNA in the control group were 0.35 ± 0.18 and 0.62 ± 0.18, respectively, which were significantly lower than those in the model group (1.79 ± 1.79 and 1.52 ± 1.44, and drug-treated group 0.48 ± 0.34 and 0.75 ± 0.26, respectively), F values = 6.914,3.894, P values were < 0.05, the differences were statistically significant. The relative expression levels of LP, OB-R and collaten I in liver were 0.71 ± 0.13, 0.81 ± 0.11 and 0.76 ± 0.13 in the model group, 0.97 ± 0.06, 1.04 ± 0.06, and 1.05 ± 0.04 respectively in the drug-treated group and 0.74 ± 0.05, 0.93 ± 0.05 and 0.91 ± 0.05. The F values were 15.425, 13.757 and 19.130 respectively in three groups (P < 0.001), the difference was statistically significant. Conclusion: Valsartan, an angiotensin II type 1 receptor antagonist, can reduce the expression of leptin and leptin receptor, reduce the production of TGFβ1 and collaten I, and play an anti-hepatic fibrosis effect.