肝素对大鼠Thy-1肾炎u-PA/PAI-1表达的影响

The effect of heparin on the expression of u-PA/PAI-1 in the anti-Thy1 glomerulonephritis of rat

目的 :研究尿激酶型纤溶酶原激活物 /Ⅰ型纤溶酶原激活物抑制因子 (u PA/PAI 1)在大鼠Thy 1肾炎病变进展过程中的变化 ,以及肝素对其表达的影响。方法 :以抗Thy 1单抗成功制备大鼠Thy 1肾炎模型 ,并用肝素对其进行治疗 ,分别于 1、3、7、14、2 1、2 8d处死动物并分别取其肾皮质。应用RT PCR及Westernblot方法检测肾皮质u PA/PAI 1mRNA及蛋白表达的变化 ,以观察肝素对其表达的影响。结果 :RT PCR法显示肾炎模型组 (G组 )于 3～ 2 8d的肾皮质u PAmRNA和 3～ 2 1d的肾皮质PAI 1mRNA的表达均高于对照组 (P <0 0 5或P <0 0 1) ;肝素治疗组 (H组 )仅 2 1d时肾皮质u PAmRNA的表达高于G组 (P <0 0 5 ) ,而PAI 1mRNA的表达于 3～ 2 8d时均低于G组 (P <0 0 5 )。Westernblot结果显示 3～ 2 8d时 ,G组u PA和PAI 1蛋白表达量高于对照组 (P <0 0 5或P <0 0 1) ,这与RT PCR检测结果相似 ;H组肾皮质u PA蛋白表达量与G组相比差异无显著性 ,而 3～ 2 1d时PAI 1蛋白表达量均低于G组 (P <0 0 5或P <0 0 1)。结论 :大鼠Thy 1肾炎肾皮质u PA与PAI 1的表达均随肾小球病变的进展而增强 ,肝素治疗可能通过干扰或抑制u PA和PAI

Purpose To investigate the changes of u-PA/PAI-1 expression and the effects of heparin on u-PA/PAI-1 expression in the development and progression of rat anti-thy1 glomerulonephritis. Methods Anti-thy1 glomerulonephritis model was produced in rats by injecting anti-thy1 monoclonal antibody. Heparin was used for the treatment of this model. Renal samples were obtained from sacrificed rats 1,3,7,14,21,28 days after injection. The expression of u-PA and PAI-1 mRNA were measured by semi-quantitative RT-PCR method, and their proteins by Western blot analysis in kidney cortex. The effects of heparin on u-PA/PAI-1 mRNA and protein expression were also observed. Results RT-PCR method showed that in the nephritic group the expression of u-PA mRNA was higher than that in the control group from day 3 to day 28 (P<0.05 or P<0.01) and the expression of PAI-1 mRNA was higher than that in the control group from day 7 to day 21(P<0.05). In the heparin-treated group the expression of u-PA mRNA was higher than that in the nephritic group at day 21 (P<0.05) and the expression of PAI-1 mRNA was lower than that in the nephritic group from day 3 to day 28(P<0.05). Western blotting detection showed that the expression of u-PA and PAI-1 proteins in the nephritic group were much higher than that in the control group (P<0.05 or P<0.01) from day 3 to day 28. There was not significant difference of u-PA protein expression between the heparin-treated group and the nephritic group (P>0.05). The expression of PAI-1 protein in the heparin-treated group was much lower than that in the nephritic group from day 3 to day 21(P<0.05 or P<0.01). Conclusions The expression of u-PA and PAI-1 on kidney tissue are increased with the glomerular lesions. It is suggested that the inhibitory effect of heparin on the u-PA and PAI-1 expressions is related to anti-proliferative reaction in rat anti-thy1 glomerulonephritis.