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氯通道阻滞剂NPPB对人肾小球系膜细胞增殖的抑制作用

Inhibitory effects of chloride channel blockers NPPB on proliferation of human glomerular mesangial cells

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【作者】 焦军东岳朋杜智敏董德利艾静杨宝峰

【Author】 JIAO Jun-dong 1, YUE Peng 1, DU Zhi-min 2, DONG De-li 1, AI Jing 1, YANG Bao-feng 1*(1. Department of Pharmacology, Harbin Medical University, Bio-pharmaceutical Key Laboratory of Heilongjiang Province, 2. Department of Clinical Pharmacology, Harbin Medical University, Harbin 150086, China)

【机构】 哈尔滨医科大学药理学教研室哈尔滨医科大学临床药理教研室哈尔滨医科大学药理学教研室 黑龙江生物医药工程重点实验室黑龙江哈尔滨150086黑龙江生物医药工程重点实验室黑龙江哈尔滨150086

【摘要】 目的研究氯通道阻滞剂5硝基2(3苯丙胺)苯甲酸[5nitro2(3phenylpropylamino)benzoicacid,NPPB]对肾小球系膜细胞增殖的作用及可能的机制。方法细胞计数和3HTdR参入量测定确定细胞增殖,应用流式细胞术检测细胞周期时相。结果与对照组相比,氯通道阻滞剂NPPB和细胞外高渗透压力使人肾小球系膜细胞数和3HTdR参入量明显减少,并呈剂量依赖关系,但不增加系膜细胞乳酸脱氢酶释放量。NPPB使细胞周期停滞在G0/G1期。结论氯通道阻滞剂NPPB对人肾小球系膜细胞增殖有抑制作用,其机制与细胞容量改变有关。

【Abstract】 Aim To investigate the effects of NPPB, a chloride channel blocker, on proliferation of mesangial cells. Methods Cell proliferation was determined by measuring cell number and 3H-thymidine incorporation. The LDH activity released from these cells was measured as evaluation of cell viability. The phase of cell cycle was detected by flow cytometry. Results Cell proliferation assays showed that treatment with both NPPB (50 and 25 μmol·L -1) and in hypertonic media (100% increased osmolarity with D-mannitol ) significantly reduced the number of human MC and 3H-thymidine incorporation in a dose-dependent manner. But the LDH activity was not significantly altered in the treatment with 50 μmol·L -1 NPPB. Flow cytometry experiments showed that 50 and 25 μmol·L -1 NPPB arrested ( 84.2±2.4)% and (80.8±2.9)% of cells at G0/G1 stage, versus (70.5±1.4)% of control cells. Conclusion NPPB suppresses cell proliferation and produces growth arrest at G 0/G 1 phase in human MC by a mechanism probably associated with changes in cell volume.

【基金】 国家自然科学基金资助项目(30070925,30371647);黑龙江省科技攻关项目(GC03C6153).
  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2005年08期
  • 【分类号】R96
  • 【被引频次】4
  • 【下载频次】156
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