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The Study Of Cytochrome C, Caspase-3Change In Chronic Hepatitis B Of Liver Inflammation And Fibrosis

Posted on:2014-01-11Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhengFull Text:PDF
GTID:2234330398976851Subject:Infectious diseases
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BACKGROUNDViral hepatitis B has the route of transmission is complex, infectivity is strong, with high incidence rate, etc.Not only can cause acute hepatitis, chronic hepatitis, and liver fibrosis and hepatocellular carcinoma (HCC) is closely related to the occurrence and development.. C Recurrent episodes of chronic hepatitis b, is not more and can be transformed into liver fibrosis (LF). The key to sustainable development of liver fibrosis that liver cell injury and necrosis of the surrounding non-parenchymal cells continuously stimulated, which led to the synthesis and deposition of extracellular matrix degradation rate exceeds the liver cells, resulting alteration and destruction of liver tissue structure eventually develop into cirrhosis.Apoptosis-related genes, the hepatitis viruses, the molecules of cells, autoimmune and other factors involved, so far the treatment of hepatitis B is still difficult and hot facing in the world of today. Hepatitis B virus (HBV) invade the body, not only infect the host liver cells, at the same time involved in activation of cytotoxic T lymphocytes (CTL) by direct damage or by the immune response induced hepatocyte apoptosis or necrosis. Hepatocyte apoptosis is a complex process, more than one gene regulation of each gene through the interaction of some of the intermediate links, the combined effect of the implementation of the apoptosis. Various cytokines (such as cytochrome C, Caspase-3, the serum levels of tumor necrosis factor) through the complex regulatory mechanism of apoptosis in viral hepatitis, liver fibrosis plays an important role. In the past, the people did not think that apoptosis play a role in fibrosis generated research has focused on liver fibrosis caused liver damage in hepatocellular necrosis, little attention associated with liver cell apoptosis and it role in the pathogenesis of hepatic fibrosis, but in fact involved in liver fibrosis apoptotic response. Hepatocyte apoptosis is a two-way, it is the body to fight cancer, infections and protection measures to prevent autoimmune reactions, but a lot of hepatocyte apoptosis is often accompanied by liver cell necrosis, can cause liver damage structure and function. Prevent liver cell apoptosis can often prevent necrosis. Apoptosis inhibitor can be used to interfere with the development of liver fibrosis.Hepatocyte apoptosis can affect the liver inflammation and fibrosis, however under different degree of liver fibrosis and inflammation change relationship between the apoptosis effect how, the report is less.Cytochrome C and Caspase-3endogenous and exogenous apoptosis apoptotic factors, the study of this disease from the molecular level, in order to study cytochrome C, caspase-3in chronic hepatitis B virus expression of hepatitis patients with different pathological grade and stage of fibrosis, liver inflammation grade and fibrosis staging two apoptotic factors, a deeper understanding of the process of liver pathology hepatocyte apoptosis signal transduction changes, analysis of endogenous apoptosis pathway and extrinsic apoptotic pathway in patients with chronic hepatitis B status and provide a theoretical basis for the treatment of chronic hepatitis B.OBJECTIVEObservation and comparison of cytochrome C, Caspase-3expression in different grading and staging of viral hepatitis B, and to explore the variation of the two factors in the various liver inflammatory activity and the degree of fiber hyperplasia. METHODS1.Collecting cases:Collecting the cases diagnosed by viral hepatitis B that have the results of liver biopsy in the department of infectious disease of the First Affiliated Hospital of Zhengzhou University from June2010to December2012, precluding the merger of other diseases such as decompensated cirrhosis, alcoholic liver disease, fatty liver, autoimmune hepatitis, primary biliary cirrhosis, liver cancer, or consolidation of the serious heart, brain, lung, kidney and other organ parenchymal disease. At the same time10cases of normal liver tissue as control.2.Experimental method:According to different classification of the pathologist diagnosis stage, take the live liver making paraffin block, for hematoxylin-eosin HE stain. Using immunohistochemistry to detect the expression of cytochrome C and Caspase-3in liver and calculating the average gray value by software analysis system.3.Statistical analysis:using statistical software SPSS17.0and EXCEL2007for data analysis. Measurement data expressed as a mean±standard deviation(x±s). Comparing the expression of apoptotic factors with different pathological grading and staging by Wilcoxon Test, and using the Spearman rank correlation analysis to search for the relationships between apoptotic factors and liver pathological stages of chronic hepatitis B.RESULTS1.The positive expression rate of Cytochrome C, caspase-3in patients with chronic hepatitis B was73%、68.5%respectively, The positive rate in control was20%、20%respectively, they showed great significant difference(P<0.005)..2.The Wilcoxon Test points out that the differences between the expression of cytochrome C and5groups of pathological grading has statistical significance (P <0.05). Also the test points out that the differences between the expression of cytochrome C and5groups of pathological grading has statistical significance t in the same stage of fibrosis.3.The Wilcoxon Test points out that the differences between the expression of cytochrome C and5groups of pathological staging has statistical significance (P <0.05). Also the test points out that the differences between the expression of cytochrome C and5groups of fibrosis has statistical significance t in the same stage of pathological grading.4.The Wilcoxon Test points out that the differences between the expression of Caspase-3and5groups of pathological grading has statistical significance(P<0.05). Also the test points out that the differences between the expression of Caspase-3and5groups of pathological grading has statistical significance t in the same stage of fibrosis.5.The Wilcoxon Test points out that the differences between the expression of Caspase-3and5groups of pathological staging has statistical significance(P<0.05). Also the test points out that the differences between the expression of Caspase-3and5groups of fibrosis has statistical significance t in the same stage of pathological grading.6. Cytochrome C, Caspase-3expression in the liver tissue of patients with chronic hepatitis B there is a clear correlation (P<0.05). There were highly correlations between Cytochrome C、Caspase—3in liver tissue of chronic hepatitis B (P<0.05).7. Logistic regression analysis showed that the liver inflammation and fibrosis are risk factors for hepatocyte apoptosis.CONCLUSIONDifferent liver pathologic stage of cytochrome C expression level is different, cytochrome C associated with the degree of liver inflammation and fibrosis;different liver pathology grading Caspase-3expression levels of different Caspase-3and inflammation and fibrosis of the liver,showed that in patients with chronic hepatitis B, with the increasing level of inflammation or fibrosis, have to extrinsic pathway of apoptosis and intrinsic pathway has a significant effect on promoting endogenous and exogenous apoptotic pathway inmay play an important role in the progression of liver pathology, provide a theoretical basis for clinical treatment.
Keywords/Search Tags:cytochrome C, Caspase-3, inflammatory, fibrosis, viral hepatitis B
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