| Liver fibrosis (LF) is the result of the liver excessive synthesis and deposition of fibrous tissue and extracellular matrix (ECM) in the liver. It is the common pathologic basis of a variety of chronic liver disease developing to liver cirrhosis, the final clinical performance in end-stage liver disease. It is well known that hepatic stellate cell (HSC) is the key cell and plays a important role in the development of the liver fibrosis.It has been confirmed that liver tissue existed renin - angiotensin system (RAS) that could be closely related to the developmeat of liver cirrhosis. The roles of RAS in pathogenesis of liver fibrosis has become the one of focuses of research fields in recent years. AngiotensinⅡ(AngⅡ) is the most important bioactive substances of the system. The mechanisms of pathogenesis of AngⅡhas been gradually clarified in heart and kidney fibrosis, Angiotensin-converting enzyme inhibitors (ACEIs) and AngⅡtype 1 receptor blockers(ARBs) have been widely used in treatment of heart and kidney fibrosis in clinic. Present studies have found that AngⅡplayed a variety of pathophysiological role in the onset and development of liver fibrosis and that human HSC can express type 1 receptor of AngⅡ(AT1R) through which AngⅡplays its biological activities on HSCs. In China, Chronic hepatitis B virus infection is the main cause of chronic injury of liver.The activation of RAS could make this kind of injury sustained and aggravated. AngⅡcould cause activation, proliferation and contraction of HSCs which can synthesis and secret large amounts of growth factors, such as transforming growth factor-β(TGF-β) and platelet-derived growth factor (PDGF). These growth factors can promote the synthesis and secretion of AngⅡand eventually lead to the formation of hepatic fibrosis and even cirrhosis.In China , chronic hepatitis B , which is caused by the infection of hepatitis virus type B(HBV), is the main cause of hepatic cirrhosis and very common in Chinese population. It is one of the most serious and harmful infectious diseases to people's health. In clinic, it would be difficult to judge the extends and stages of liver lesions because of the complicated pathophysiological process and clinical manifestations. So far, there have been a lot of studies about the relationships between serum HBV DNA and liver pathology grade, but the results of these studies are inconsistent, and studies about the relationships between serum HBVDNA and the expression of AT1RmRNA have not been reported.There is no satisfactory anti-hepatitis B virus treatment at present, and single anti-virus treatment often fails to improve symptoms of the patients with chronic liver disease. Therefore, it seemed to be more important to look for a therapy of anti - hepatic fibrosis. Today, there is not any reports about effective anti-hepatic fibrosis by western medicine, and the traditional chinese medicine is still the main treatment. In this study, there would be a great significance in exploring the probability of anti-hepatic fibrosis by Western medicine. Animal experiments have shown that ACEIs and ARBs (such as Losartan) have the efficiency of reducing or delaying the formation of hepatic fibrosis. However, the probability for clinical use of this kind of medicine in human hepatic fibrotic dieseases is not clear.Objective: So far, studies about expression and distribution of AT1R in human liver tissue have rarely been seen in China. This study explored the AT1R's expression at different stages of type B virus chronic hepatitis, from the state of type B virus carriers to different stages of liver cirrhosis. The knowledges of this study could provide the probability for useing ACEIs and ARBs in treatment of liver fibrosis. This clinic study explored relationships in between serum HBV DNA, expression of AT1R mRNA and liver fibrosis.Methods: Sixty seven cases in total were enrolled in our study. Of these cases, 42 were liver biopsy specimens by liver punctures during the hospitalization in the department of gastroenterology from January 2007 to January 2008 because of chronic hepatitis B virus infection , 13 were liver tissue samples of cirrhotic patients of chronic hepatitis B from liver operations, and the other 12 were normal liver tissue from liver leaf excision because of hepatic hemangioma in the same period. Four milliliters of fast serum samples from the 67 patients were obtained 2 days around liver biopsy or surgery. According to the diagnostic criteria of Chronic hepatitis and fibrosis stages in programme to combat viral hepatitis 2000, we divided the selected cases into 4 groups: S0-1, S2-4, end stage of cirrhosis group and normal control.Pathological classification in optical microscope were made through HE and Masson stainings of the liver tissues by paraffin sections. Expression of AT1R in liver tissue were examined by immunohistochemistry(IHC) and gel electrophoresis semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). We made serum HBV DNA quantitative testing with fluorescence quantitative PCR .Results:1 The expression of AT1R in liver tissueIHC showed that positive staining of AT1R was yellow or brown in cytoplasm. Positive cells were mainly located in Disse space around sinusoid. The shapes of these cells were elliptical or irregular, with apophysises entering into liver cells, indicating HSCs. Most of the cells were scatteredly distributed, and also some of them were clustered. Expressions of AT1R were significantly increased parallel to the aggravated fibrosis. AT1R were expressed in S0-1, S2-4 and end stage cirrhosis, but it was weak or no expression in normal liver tissue.Expressions of AT1R in S0-1 group,S2-4 group and end stage of cirrhosis group were significantly increased as compared to normal control group ( P<0.01) ; There were no statistic differences between S0-1group and normal control group( P>0.05);S0-1 and S2-4 group were significantly different (P<0.01);S0-1 group and end stage of cirrhosis group were significantly different (P <0.01);S2-4 group and end stage of cirrhosis group were significantly difference,(P <0.05 ).2 The expression of AT1RmRNA in liver tissueExpressions of AT1RmRNA in S0-1 group,S2-4 group and end stage of cirrhosis group were significantly increased as compared to normal control group,There were statistic differences (P<0.01);S0-1 group and the normal control group were no significant difference (P> 0.05), S0-1 group and S2-4 group were significantly different (P <0.01), S0-1 group and end stage of cirrhosis group were significantly different (P <0.01); S2-4 group and end stage of cirrhosis group were significantly different (P <0.01).3 The correlation analysis between serum HBV DNA and liver fibrosis stageThere was no correlation between HBV DNA level and liver fibrosis stage ( r=-0.140, P>0.05).4 The correlation analysis between serum HBV DNA and AT1R mRNAThere was no correlation between HBV DNA level and AT1RmRNA (r=-0.014,P>0.05).Conclusions:1 The AT1R and AT1RmRNA were weak or no expression in normal liver tissue,but their expression were increasing in the fibrosis and cirrhosis, and the intensity of its expression was closely related to fibrosis stage.2 There were no significant correlation between Serum HBV DNA and liver fibrosis stage.3 There were no significant correlation between Serum HBV DNA and AT1RmRNA in liver tissue. |
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