| Background and ObjectiveLiver injury is closely correlated with hepatic fibrosis. Hepatic fibrosis is the common result of liver injury from diverse origins. The sequence of response to injury is local inflammation followed by recruitment and local proliferation of myofibroblast like cells and excessive deposition of extrcellular matrix. Hepatic fibrosis is a reversible and common pathological consequence of various chronic liver diseases which can eventually lead to hepatic cirrhosis that has no effective treatment at this point. Therefore it represents a common and difficult clinical challenge for the gastroenterologists worldwide in the recent 20 years. Although we have made great progresses on the study of liver fibrosis, its pathogenesis is still poorly understood in the past decades.As the complexity of hepatic fibrosis pathogenesis becomes increasingly apparent, the tools available to clarify its regulation also need to be advanced. cDNA microarray technology is a powerful descriptive method for examing the expression profile of hundreds to thousands of genes in unison. Dr. Fodor from Affymetrix company in US firstly developed the gene chip technology in the early 1990's. Since then it has been used successfully in various area of gene function research. Large scale gene expression profiling using cDNA arrays has become one of the most fruitful methods for characterizing the physiological and pathological processes. But the research of DNA chip technology in acute and chronic liver injury is scarce. Using this technique to look for differently expressed genes during the acute and chronic liver injury will be helpful for the analysis of the mechanism, clinical diagnosis and treatment of the acute and chronic liver injury. In this study, we have screened the genes associated with the acute and chronic liver injury and preliminaryly studied their functions in the hepatic fibrosis. Four sections were included in our experiments: 1) to screen the related genes with acute liver injury by means of cDNA microarray; 2)to identify the related genes with hepatic fibrosis with cDNA microarray; 3) to verify the expression of the genes related with mitogen-activated protein kinase (MAPK) signal pathway in the development of hepatic fibrosis; 4) to investigate the effects of extracellular signal-regulated kinases (ERK) on the function of the rat hepatic stellate cells.Methods1. Screening of the acute liver injury related genes with cDNA microarray30 male Sprague-Dawley (SD) rats were randomly divided into four groups: 1)surgery model group(n=10); 2) surgery control group(n=10); 3) carbon tetrachloride (CC14) model group(n=5); 4) CCl4 control group (n=5). The model of rat acute liver injury was induced by 95% hepatectomy and by subcutaneous injection of 60% CCl4 in olive oil respectively. Surviving animals were killed 48 hr after 95% liver resection and administration of CCl4. The cDNA probes were established by labelling the mRNA isolated from the rat liver. Hybridization were conducted by using a cDNA array representing 1 176 cDNA clusters and image analysis was performed to study the relationship between the two differential expression profiles of injured rat liver. In addition, we compared the ALT, AST, PT and pathology of acute injury model groups with that of control groups. Some genes were selected from a pool of differently expressed genes and subjected to semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) to further confirm the results from the microarray hybridization.2. Identification of the hepatic fibrosis related genes with cDNA microarray 85 male SD rats were randomly divided into four groups: 1) DMN model group(n=20); 2) DMN control group (n=5); 3) CCl4 model group (n=30); 4) CCl4 control group(n=5) . Hepatic fibrosis was induced by subcutaneous injection of DMN and CCl4 respectively. Rats were executed for study at the end of one, two, three weeks in DMN group and at the end of two, four, six, eight weeks in CCl4 group. The mRNA was isolated from the...
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