标题：多聚二磷酸腺苷(ADP)核糖聚合酶-1介导高糖

      作者：致大鼠肾脏系膜细胞 tPA/PAI-1的紊乱
    朱恒梅，祝胜郎*，陈结慧，叶 玲，蒋 莹，李向阳
(深圳市第六人民医院肾内科，广东 深圳 510082)

      卷次： 2012年23卷20期

      【摘要】 目的 探讨多聚二磷酸腺苷(ADP)核糖聚合酶-1 (PARP-1)在高糖(25 mmol/L)作用下大鼠肾脏
系膜细胞 tPA/ PAI-1纤溶系统紊乱中的作用。方法 (1)体外培养大鼠肾脏系膜细胞株(MCs 1097)，使用高糖
(25 mmol/L)处理大鼠肾脏系膜细胞，部分实验组中应用PARP-1特异性抑制剂PJ34 (3×10-6 mol/L)进行干预处
理。(2) RT-PCR及Western blot检测PARP-1的mRNA及蛋白表达。(3)高通量比色测定法检测PARP-1的活性。
(4) ELISA法测定细胞上清液 tPA、PAI-1的分泌蛋白。结果 (1)高糖显著诱导大鼠肾脏系膜细胞 PARP-1
mRNA和蛋白的表达，PJ-34可明显抑制高糖诱导的PARP-1 mRNA和蛋白的过度表达。同时，高糖显著诱导大
鼠肾脏系膜细胞PARP-1激活，PJ-34可显著抑制高糖诱导的PARP激活。(2)高糖轻度减少大鼠肾脏系膜细胞分
泌型 tPA的蛋白表达，显著增加大鼠肾脏系膜细胞分泌型PAI-1的蛋白表达，导致 tPA/PAI-1比值降低，PJ-34显
著预防高糖诱导的上述改变。结论 高糖可以诱导培养的大鼠肾脏系膜细胞内PARP激活，PARP1表达增加，
PJ-34预处理可以明显降低高糖诱导的大鼠肾脏系膜细胞内PARP的激活以及下游 tPA/PAI-1纤溶系统紊乱，提
示高糖可能通过过度激活PARP来诱导 tPA/PAI-1功能紊乱。

      【关键词】 系膜细胞；PARP；高糖；tPA/PAI-1；纤溶系统

      【中图分类号】 R-322 【文献标识码】 A 【文章编号】 1003—6350（2012）20—018—04<

br>Effect of Poly (ADP-ribose) Polymerase-1 in high glucose-induced disorder of of tPA/PAI-1 in rat mesangial
cells.
ZHU Heng-mei, ZHU Sheng-lang, CHEN Jie-hui, YE Ling, JIANG Ying, LI Xiang-yang. Department of
Nephrology, the Sixth Hospital of Shenzhen City, Shenzhen 510082, Guangdong, CHINA

【Abstract】 Objective To investigate the role of Poly (ADP-ribose) Polymerase-1 (PARP-1) in high glu-
cose-induced disorder of tPA/PAI-1 in rat mesangial cells (RMCs). Methods RMCs were constructed and then treat-
ed with or without high glucose (25 mmol/L). In some experimental groups, cells were pre-treated with PARP-1 inhib-
itor PJ34 (3×10-6 mol/L). RT-PCR was employed to detect the expression of PARP-1 mRNA, Western blot was used to
detect the expression PARP-1 protein, and Colorimetric assay for its activity. Meanwhile, tPA and PAI-1 protein secre-
tion were examined by ELISA. Results High glucose significantly stimulated the overexpression of both PARP-1
mRNA and protein in RMCs. At the same time, high glucose obviously stimulated PARP-1 activation, and PJ34 effec-
tively inhibited the activation of PARP-1. Also, PJ34 suppressed high glucose-induced downregulation of tPA protein se-
cretion, upregulation of PAI-1 protein secretion and reversed the reduction of tPA/PAI-1 ratio. Conclusion PARP-1
mediates high glucose-induced disorder of tPA/PAI-1 in rat mesangial cells.

      【Key words】 Mesangial cells; PARP; High glucose; tPA/PAI-1; Fibrinolytic system
·实验研究·