| Backgroud: The portal hypertension(PHT), which mostly occurred in various types of liver cirrhosis, especially in decompensations, had many clinical manifestations including establishment of collateral circulation, accumulation of fluid in the peritoneal cavity and splenomegaly. Gastrointestinal hemorrhage, the most life-threatening complication due to PHT, is an urgent clinical problem because of its high incidence and large risk.Now increasing portal vascular resistance and more portal blood flow are recognized as pathogenesis of liver cirrhosis with PHT. Drug therapy can lower portal vascular resistance by intrahepatic vasodilation,or reduce blood flow by visceral vasoconstriction, and then it can lower portal venous pressure. Valsartan, a new type of angiotensinⅡreceptor blocker(ARB), can inhibit directly various physiological role of Ang-Ⅱby blocking the combination of Ang-Ⅱwith its specific receptor. To some extent it can be used as a remedy of PHT owing to its reducing portal venous pressure and liver cirrhosis by modulating the concentration of vasoactive substances and improving the indexes of liver fibrosis.Objective: To explore effects of valsartan on vasoactive substances such as endothelin (ET), nitric oxid(NO), tumor necrosis factor-alpha(TNF-α) and the indexes of liver fibrosis including transforming growth factor-beta1(TGF-β1), cholylglycine(CG), hyaluronic acid(HA) in liver cirrhosis patients with PHT.This thesis maked a further study on the therapeutic effects of valsartan on PHT in patients with liver cirrhosis.Methods: Thirty-six liver cirhosis patients with PHT were randomized into two groups: treatment group(n=18) and control group(n=18). The control group were treated with routine treatment for 1 month, while the treatment group were given valsartan 80mg/d plus routine treatment for 1 month. Before and after the treatment, fasting peripheral venous blood were taken for further study of ET, TNF-α, CG and HA with radioimmunoassay. Serum NO concentration was measured by the method of nitric acid reductase, and serum TGF-β1 by enzyme-linked immunosorbentassay(ELISA). During the whole observation period, the blood pressure, heart rate of all the patients were observed, and blood routine, liver and renal functions were monitored.Results:①In therapy group, the levels of ET, NO and TNF-αwere lower than that before treatment respectively,the differences were all significant(P<0.01). But in control group, although the levels of ET, NO and TNF-αwere lower than that before treatment, there was no statistically significant difference(P>0.05). There were significant differences in ET, NO and TNF-αbefore and after treatment between two groups(P<0.01).②After treated with valsartan, the levels of TGF-β1, CG and HA were lower respectively than that before treatment(P<0.01). While the levels of TGF-β1, CG and HA were lower than that before treatment in control group, there were no statistically significant difference(P>0.05). The difference of TGF-β1,CG and HA before and after treatment were statistically significant between two groups(P<0.01).③After the application of valsartan,blood pressure and heart rate in patients didn't changes obviously, and blood routine examination, liver and renal functions weren't worsen significantly.Conclusions: Valsartan could lower portal vascular resistance and decrease portal venous flow by adjusting the concentration of vasoactive substances, such as ET,NO, TNF-α, so that it could reduce portal venous pressure.Valsartan may eliminate autocrine role in the positive regulation of TGF-β1 via blocking the combination of Ang-Ⅱwith AT1R located in the surface of HSC. Thus, it could not only deter liver fibrosis, but reduce portal venous pressure indirectly.Valsartan could reduce portal venous pressure and improve liver fibrosis, at the same time, it had no significant side effect to blood pressure or heart rate, moreover, liver and renal functions aslo weren't damaged significantly. |
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