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用CCl_4诱发大鼠肝纤维化,检测不同期大鼠血清和肝组织匀浆中层粘素(Laminin,LN)的含量,用免疫组化法观察LN在肝脏内的沉积。结果表明,血清LN水平在反映肝组织渐进性损伤方面较之肝内LN含量理想;肝内LN含量在肝受损晚期升高,与免疫组化结果平行。检测不同肝病患者血清LN含量,肝硬化LN水平明显高于正常人和非硬化患者;免疫组化观察慢性肝病和肝硬化患者肝内LN分布,结果以后者LN沉积为多。体外培养大鼠肝细胞,研究LN对细胞的增殖和胶原合成的影响,提示生理血清浓度的LN对肝细胞代谢无明显影响,高浓度时抑制其DNA及胶原的合成。提示肝硬化时LN合成明显增加,血清LN水平是判断肝脏活动性损伤和纤维化进程的良好指标,可适于肝硬化的早期诊断。肝内LN大量沉积,预示肝损伤发展至晚期肝硬化,同时大量增多的LN对肝细胞进一步合成胶原有负反馈抑制作用。
Liver fibrosis was induced by CCl_4 in rats. The levels of laminin (Laminin, LN) in serum and liver homogenates of rats at different stages were measured. The deposition of LN in the liver was observed by immunohistochemistry. The results showed that the level of serum LN was better than that in the liver in reflecting progressive injury of liver tissue. The content of LN in liver increased in the late stage of liver damage, which was in parallel with the result of immunohistochemistry. Detecting serum levels of LN in patients with different liver diseases, liver cirrhosis LN levels were significantly higher than normal and non-sclerotic patients; immunohistochemistry observed in patients with chronic liver disease and liver cirrhosis LN distribution, the results were more LN deposition. In vitro, rat hepatocytes were cultured to study the effects of LN on cell proliferation and collagen synthesis, suggesting that LN at physiological serum concentrations had no significant effect on the metabolism of hepatocytes and inhibited DNA and collagen synthesis at high concentrations. Suggesting that LN synthesis increased significantly in patients with cirrhosis, serum LN level is to determine the activity of liver damage and fibrosis process a good indicator of liver cirrhosis can be suitable for early diagnosis. A large number of intrahepatic LN deposition, indicating the development of liver injury to advanced cirrhosis, while a large number of increased LN on the liver cell collagen synthesis further negative feedback inhibition.