Protective And Therapeutic Effect Of Telmisartan On Hepatic Fibrosis In Experimental Rats

Objective:To investigate prophylactic and therapeutic effect and mechanism of Telmisartan on hepatic fibrosis induced by CCl4 in experimental rats.Methods: Total 40 homologous series male SD rats were randomly divided into 3 groups, i.e., normal control group (12), CCl4 model group (12) and intervened group by Telmisartan (16). The liver fibrotic model was induced by CCl4 i.p for 5wk. Telmisartan was given at the same time model establishment in each intervened group by administration lasted for 6wk. Decollate to get the blood of all rats after 7 weeks . ALT,AST and ALB of serum was detected by automatic biochemistry equipment. Hyaluronic acid was detected by ELISA detection. Liver and spleen was obtained to calculate the index. The liver pathological changes were observed in each group of rats after HE staining to evaluate the therapeutic effect of Telmisartan; TGF-β1,PPAR-γand PDGF of liver tissue was detected by the method of immunohistochemistry respectively; The mRNA expression of TGF-β1,MMP-1,TIMP-1,α-SMA,PPAR-γand iNOS was detected by RT-PCR detection, respectively. The statistical method of two-sample/group t-test was executed by SPSS13.0 software and all the data was expressed in mean±( x±s).Results: In the process of preparing model, we have observed the general state of health of model group ware badly and weight gain ware slower than other two groups. The mean of liver index of model group is 4.85±0.42, of normal control is 2.92±0.41 and of intervened group is 3.09±0.36 , The mean of liver index of model group compares with normal control and Telmisartan groups respectively, the statistic significance is significant difference(P<0.01and P<0.01); Liver tissue HE staining observed by microscope indicated the hepatic fibrosis degree in only CCl4 rats was more severe than in rats of normal control and Telmisartan group, the mean of hepatic inflammatory activity scores of model group is 18.6±2.1, of normal control is 0.0±0.0 and of Telmisartan group is 8.6±1.9, compared with normal control and Telmisartan groups respectively, the statistic significance is significant difference(P<0.01and P<0.01), the mean of hepatic fibrosis scores of model group is 14.5±1.6, of normal control is 0.33±0.49 and of Telmisartan group is 7.7±1.7, compared with normal control and Telmisartan groups respectively, the statistic significance is significant difference(P<0.01and P<0.01); The average content of serum HA of model group increased obviously , compared with normal control and Telmisartan groups, the mean of model group is 72.2±2.1 ng/ml, normal control is 35.5±4.6 ng/ml and Telmisartan groups is 49.7±6.1ng/ml, the statistic significance is significant difference(P<0.01and P<0.01); The immunohistochemistry staining indicated TGF-β1and PDGF were powerfully positive in rats liver tissue of model group, but PPAR-γwas negative and TGF-β1 and PDGF were leptopositive or negative in other groups, PPAR-γwas positive in normal control group and powerfully positive in Telmisartan group; RT- PCR detection indicated the mRNA expressed amount of TGF-β1,TIMP-1 andα-SMA in model group all increased obviously contrast to other groups, the TGF-β1,TIMP-1 andα-SMA average gray scale are significant statistic significance compared with of other two groups(P<0.01and P<0.01). MMP-1,PPAR-γand iNOS were all lower in model group than other groups, the MMP-1,PPAR-γand iNOS average gray scale are significant statistic significance compared with of other two groups(P<0.01and P<0.01).Conclusions: the protective and therapeutic effect of Telmisartan on hepatic fibrosis in experimental rats is effective。Its mechanism of action is Telmisartan can activate PPAR-γas well as blocking the angiotensinПacceptor-1(AT-1) and suppress the express of TGF-β1,TIMP-1 andα-SMA in rat's liver tissue, depress the hyperplasy and activation of HSC accordingly,. up-regulate the iNOS express in infl-liver tissue at the same time.