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为探讨转录因子活化子蛋白１（ＡＰ－１）和相关的信号转导分子在凝血酶诱导人肾小球系膜细胞纤溶酶原激活物抑制物１（ＰＡＩ－１）表达中的作用，采用纤维蛋白平板法、Ｎｏｒｔｈｅｒｎ杂交、凝胶电泳阻滞实验（ＥＭＳＡ）和Ｗｅｓｔｅｒｎ杂交方法，分别检测凝血酶刺激培养的人肾小球系膜细胞ＰＡＩ－１蛋白质活性和ｍＲＮＡ表达情况，以及ＡＰ－１ＤＮＡ连接活性和ＡＰ－１组成蛋白质ｃ－Ｊｕｎ、ｃ－Ｆｏｓ量的变化。结果发现：①凝血酶呈浓度依赖性的方式促进肾小球系膜细胞ＰＡＩ－１蛋白质活性和ｍＲＮＡ表达，其效应能被凝血酶的特异性拮抗剂水蛭素阻断；②凝血酶能明显促进转录因子ＡＰ－１的ＤＮＡ连接活性；③ｃｕｒｃｕｍｉｎ、ｓｔａｕｒｏｓｐｏｒｉｎｅ和ｇｅｎｉｓｔｅｉｎ均能在不同程度上抑制ＡＰ－１的ＤＮＡ连接活性，并进而部分逆转凝血酶上调系膜细胞ＰＡＩ－１ｍＲＮＡ表达的效应。研究表明，转录因子ＡＰ－１在凝血酶上调人肾小球系膜细胞ＰＡＩ－１表达的信号转导过程中起着重要的作用，蛋白激酶Ｃ和蛋白酪氨酸激酶可能是凝血酶介导系膜细胞ＡＰ－１活化及ＰＡＩ－１表达的上游信号。
To explore the role of transcription factor activator protein 1 (AP-1) and related signal transduction molecules in thrombin-induced expression of plasminogen activator inhibitor-1 (PAI-1) in human mesangial cells, The activity and mRNA expression of PAI-1 in cultured human glomerular mesangial cells stimulated by thrombin were detected by fibrin plate method, Northern hybridization, gel electrophoresis retardation assay (EMSA) and Western blotting, and the expression of AP- 1 DNA ligation activity and AP-1 protein c-Jun, c-Fos changes. The results showed that: (1) thrombin promoted the PAI-1 protein activity and mRNA expression in mesangial cells in a concentration-dependent manner, the effect of which was blocked by hirudin, a specific antagonist of thrombin; (2) thrombin (3) Both curcumin, staurosporine and genistein can inhibit the DNA-binding activity of AP-1 to a certain extent and partially reverse the effect of thrombin up-regulation of PAI-1 mRNA expression in mesangial cells. Studies have shown that the transcription factor AP-1 plays an important role in the signal transduction of PAI-1 induced by thrombin in human glomerular mesangial cells. Protein kinase C and protein tyrosine kinase may be mediated by thrombin Mesangial cell AP-1 activation and PAI-1 expression of the upstream signal.