The Effects of Candesartan and Benazepril on Expression of ACE2 and Ang-(1-7) of Hepatic Fibrosis in Rats
|Course||Digestion within the science|
|Keywords||Hepatic fibrosis Candesartan Benazepril ACE2 Ang-(1-7)|
Objective:To explore the protective effects of angiotensinⅡtype 1 receptor blocker candesartan and angiotensin converting enzyme inhibitor benazepril on hepatic fibrosis induced by chronic carbon tetrachloride （CCL4） in rats, and to observe the influences on angiotensin converting enzyme2（ACE2） and angiotensin-（1-7）[Ang-（1-7）]. So as to seek and enrich effective methods for clinical treatment of liver fibrosis.Methods:Hepatic fibrosis was induced by intraperitoneal injection of chronic carbon tetrachloride （CCL4） in rats. 55 Wistar male rats were randomly divided into four groups, normal control group（12 rats）, model group（15 rats）, benazepril treatment group（14 rats） and candesartan treatment group（14 rats）. Except rats in control group, all were given the first intraperitoneal injections of 40 % CCL4 （5ml/kg）, then the second intraperitoneal injections of 40 % CCL4（ 2ml/kg, twice a week）. The rats in control group were given the intraperitoneal injection of the same dosage of oil. Since the first day of the intraperitoneal injection, the rats in treatment groups were given benazepril(10mg. kg-1. d-1) and candesartan(4mg. kg-1. d-1)for 8 weeks by gastric givage. The liver tissue and blood samples of all rats were examined at the end of 8 weeks. On the 42nd day（6w） and 56th day（8w）, blood samples and liver tissue were collected after the portal pressure was measured. Serum ALT was measured, and Ang-（1-7） levels were examined by enzyme-linked immunosorbent assay（ELISA）. Histopathological study of liver tissue was done with hematoxylin-eosin （HE） and Masson trichrome staining. ACE2 were evaluated by immunohistochemistry.Results:（1） Candesartan and benazepril significantly attenuated the degree of hepatic fibrosis （P<0.05）. （2） Compared with the normal group, the body weights of the rats in model group decreased（P<0.05）, the serum ALT levels increased （P<0.05）. Compared with the model group, the body weights of the rats in the treatment groups increased （P<0.05）, the serum ALT levels decreased（P<0.05）. （3） The portal pressure of the rats in model group increased （P<0.05）. Compared with the model group, the portal pressure in treatment groups decreased （P<0.05）.（4） The results of ELISA showed that the levels of Ang-（1-7） in the model group were higher than in the control group（P<0.05）, the levels of Ang-（1-7） in the treatment groups were further elevated （P<0.05）. （5） The immunohistochemical results of ACE2 indicated: compared with control group, the positive expression of ACE2 in the model group increased, and the scope expanded. Compared with model group, the positive expression of ACE2 in candesartan treatment group increased, but in the benazepril treatment group, the positive expression of ACE2 didn’t increase obviously.Conclusion:（1） This experiment further proved that angiotensinⅡtype 1 receptor blocke candesartan and angiotensin converting enzyme inhibitor benazepril could significantly attenuate the degree of hepatic fibrosis in CCL4-induced rats. （2） Benazepril and candesartan could inhibit the hepatic fibrosis, which not only could inhibit the production of AngⅡand prevent the linking of AngⅡwith its receptor, but also candesartan could increase the expression of ACE2 and the production of Ang-（1-7）, benazepril could reduce the degradation of Ang-（1-7）. In a word, the two drugs could increase the concentration of Ang-（1-7） and inhibit the development of hepatic fibrosis.