| Objective:To investigate the therapeutic effect and mechanism of telmisartan on hepatofibrosis in rats induced by CCL4.Methods:Forty male rats were randomly divided into3groups, including control group (10rats), model group (15rats) and experimental group (15rats). In the model group and experimental group (15rats), each rat was dealed with CCL4via intraperitoneal injection to induce hepatofibrosis. Meanwhile, each rat in the experimental group received telmisartan by gastric lavage daily for7weeks, then all the rats were put to death. The level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA) and laminin (LN) were analyzed. Hepatic tissue specimens were sectioned and Hematoxylin and Eosin (HE) staining and Masson staining were performed. The content of TIMP-land MMP-13in the hepatic tissue were detected by ELISA. Additionally, immunohistochemical staining of bax and bcl-2were performed on hepatic tissue. All of the data were analyzed using the SPSS17.0statistics software (SPSS Inc., Chicago, IL, USA). Quantitative data was displayed as X±s. Differences in the means of continuous data were compared by analysis of variance (ANOVA), and the X2test was used for comparisons of categorical data. A p value of<0.05was considered to be statistically significant.Results:There was no significant difference in weight between every two groups before the experiment. After the experiment, the average weight of model group decreased significantly compared with control group (250.1±26.3vs.340.9±32.7g, P<0.05), whereas there was no significant difference between experimental group and control group (320.3±45.7g vs.340.9±32.7g, P>0.05). As to the level of ALT, AST and ALB, there is significant difference between every two groups (P<0.05), suggesting that the liver fuction of the rats was injured by CCL4and partly recovered after administration of telmisartan. Meanwhile, the level of HA and LN of model group increased significantly compared with control group respectively (422.0±16.5vs.124.2±5.1ng/ml,55.9±4.5vs.20.7±3.2ng/ml, P<0.05), whereas there was no significant difference between experimental group and control group respectively (156.4±11.5vs.124.2±5.1ng/ml,36.3±5.9vs.20.7±3.2ng/ml, P>0.05), suggesting that tehnisartan had an effect of preventing hepatofibrosis. As to the content of MMP-13and TIMP-1in the hepatic tissue, there was significant difference between model group and control group (55.9±6.7vs31.9±3.3ng/ml,140.9±15.6vs15.3±1.6ng/ml, P<0.05), whereas there was no significant difference between experimental group and control group(30.4±4.6vs31.9±3.3ng/ml,18.2±1.7vs15.3±1.6ng/ml, P>0.05). The average liver index of model group was higher than that of control group(4.9±0.7vs3.4±0.3, P<0.05), but there was no significant difference between experimental group and control group(3.4±0.4vs3.4±0.3, P>0.05). As the results of HE staining revealed, the score of inflammatory activity and hepatofibrosis were higher than that of control group respectively (17.9±2.2vs.0.1±0,14.8±1.5vs0.1±0.1, P<0.05), but there was also significant difference between model group and experimental group respectively (17.9±2.2vs8.7±1.6,14.8±1.5vs7.6±1.8, P<0.05), suggesting that the severity of inflammatory activity and degree of hepatofibrosis were higher in model group and telmisartan could relieve the inflammatory activity and hepatofibrosis. As the results of Immunohistochemical staining revealed, there was significant difference between model group and control group respectively (4.7±0.3vs.1.2±0.1,5.9±0.3vs1.2±0.1, P<0.05), but there was also significant difference between model group and experimental group respectively (4.7±0.3vs3.2±0.2,5.9±0.3vs3.2±0.2, P<0.05), suggesting that telmisartan could inhibit the apoptosis of hepatic cells induced by CCL4.Conclusions:Telmisartan can relieve the inflammatory activity of liver and prevent the process of hepatofibrosis in rats induced by CCL4. It is probably because that telmisartan could inbibit the effect of angiotensin II, inhibit the proliferation of hepatic stellate cell, reduce the expression of TIMP-1and promote the degradation of extracellular matrix. |
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