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[目的]探讨肝纤维化不同分级α-平滑肌肌动蛋白(-αSMA)、基质金属蛋白酶1(MMP-1)、基质金属蛋白酶抑制剂1(TIMP-1)蛋白表达以及血浆尿激酶型纤溶酶原激活物(uPA)、纤溶酶原激活物抑制剂1(PAI-1)变化在肝纤维化发生发展中的意义。[方法]慢性肝病患者37例,依据病理变化分为0~4级,其中1级8例,2级9例,3级7例,4级13例;正常对照组6例。免疫组化法测定肝组织-αSMA、MMP-1、TIMP-1蛋白表达。ELISA法测定血浆uPA、PAI-1、转化生长因子β1(TGF-β1)变化。并同时检测血透明质酸、血清清蛋白、凝血酶原时间及其活动度、胆红素改变。[结果]随着肝纤维化的发展,肝组织-αSMA、MMP-1、TIMP-1蛋白表达以及血浆uPA、PAI-1、TGF-β1水平逐渐增加。在肝纤维化3、4级-αSMA、TIMP-1蛋白表达、血浆PAI-1水平增加尤为明显,而血浆uPA水平、肝组织MMP-1蛋白表达差异无统计学意义,表现为uPA、MMP-1相对不足。在肝纤维化4级血浆TGF-β1与-αSMA蛋白表达呈正相关(P<0.05),-αSMA蛋白表达与PAI-1、TIMP-1蛋白表达呈正相关(均P<0.05)。[结论]肝组织TIMP-1蛋白表达以及血浆PAI-1在肝硬化发展过程中发挥着重要作用。抑制TGF-β1的早期激活,抑制肝星状细胞激活与PAI-1过度表达,适当增加MMP-1表达,可能有助于增加肝细胞外基质降解,从而延缓肝硬化的发生发展。
[Objective] To investigate the expression of α-SMA, MMP-1 and TIMP-1 in different grades of hepatic fibrosis and the relationship between plasma urokinase fibrinolysis The significance of the changes of uPA and PAI-1 in the development of hepatic fibrosis. [Method] Thirty-seven patients with chronic liver disease were divided into 0 ~ 4 grades according to the pathological changes, including 8 cases of grade 1, 9 cases of grade 2, 7 cases of grade 3, 13 cases of grade 4 and 6 cases of normal control group. Immunohistochemistry was used to detect the expression of α-SMA, MMP-1 and TIMP-1 in liver tissue. The levels of uPA, PAI-1 and TGF-β1 in plasma were measured by ELISA. At the same time, hemagglutinin, serum albumin, prothrombin time and activity, bilirubin were detected. [Results] With the development of hepatic fibrosis, the expression of -αSMA, MMP-1 and TIMP-1 in liver tissues and the levels of uPA, PAI-1 and TGF-β1 in plasma gradually increased. The expression of 3,4-αSMA and TIMP-1 in liver fibrosis increased especially in plasma PAI-1, while the level of uPA in plasma and the expression of MMP-1 in liver tissue had no statistical significance, which showed uPA and MMP- 1 is not enough. There was a positive correlation between the expression of TGF-β1 and -αSMA protein in grade 4 plasma of hepatic fibrosis (P <0.05), and the expression of alpha-SMA protein was positively correlated with the expression of PAI-1 and TIMP-1 (all P <0.05). [Conclusion] The expression of TIMP-1 in liver tissue and plasma PAI-1 play an important role in the development of liver cirrhosis. Inhibition of early activation of TGF-β1, inhibition of hepatic stellate cell activation and PAI-1 overexpression, an appropriate increase in MMP-1 expression may contribute to extrahepatic extracellular matrix degradation, thereby delaying the occurrence and development of cirrhosis.