氯通道阻滞剂NPPB对人肾小球系膜细胞增殖的抑制作用氯通道阻滞剂NPPB对人肾小球系膜细胞增殖的抑制作用

目的研究氯通道阻滞剂5-硝基-2-(3-苯丙胺)苯甲酸［5-nitro-2-(3-phenylpropylamino)- benzoic acid，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³H-TdR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³H-TdR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。

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

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 micromol x 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 micromol x L(-1) NPPB. Flow cytometry experiments showed that 50 and 25 micromol x 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 G0/G1 phase in human MC by a mechanism probably associated with changes in cell volume.