肝素对大鼠Thy-1肾炎u-PA/PAI-1表达的影响

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、21、28d处死动物并分别取其肾皮质。应用RT－PCR及Western blot方法检测肾皮质u-PA/PAI-1 mRNA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3－28d的肾皮质u-PA mRNA和3－21d的肾皮质PAI－1 mRNA的表达均高于对照组（P＜0.05或P＜0.01);肝素治疗组（H组）仅21d时肾皮质u-PA mRNA的表达高于G组（P＜0.05),而PAI-1 mRNA的表达于3－28d时均低于G组（P＜0.05)。Western blot结果显示3－28d时,G组u-PA和PAI－1蛋白表达量高于对照组（P＜0.05或P＜0.01),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3－21d时PAI－1蛋白表达量均低于G组（P＜0.05或P＜0.01)。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－1的表达而发挥其治疗作用。

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

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.