钙拮抗剂对系膜细胞增殖的抑制作用  

INHIBITION OF HUMAN MESANGIAL CELL PROLIFERATION BY CALCIUM ANTAGONISTS

作　　者：高远赋[1,2] 王晓燕[1,2] 姜新猷[1,2] 贾力 

机构地区：[1]南京军区南京总医院儿科 [2]南京医科大学小儿肾脏病中心

出　　处：《肾脏病与透析肾移植杂志》1997年第2期134-138,共5页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的：观察钙拮抗剂维拉帕米、硝苯地平、恬而心，在不同浓度时对系膜细胞增殖及肥大的作用。方法：体外对人体系膜细胞进行二维培养，选第４～６代系膜细胞置９６孔培养板进行研究。用促有丝分裂剂ＰＤＧＦ（５μｇ／Ｌ）、凝血酶（５ＮＩＨｋＵ／Ｌ）促其增殖，加或不加三种不同类型钙拮抗剂：维拉帕米、硝苯地平、恬而心，观察对以上刺激的抑制作用，加入同位素３ＨＴｄＲ（１μＣｉ／孔）、３ＨＵｒ（１μＣｉ／孔）、３ＨＬｅｕ（１μＣｉ／孔），液闪计数仪测定ｍｉｎ１值。结果：经ＰＤＧＦ、凝血酶刺激后３ＨＴｄＲ掺入系膜细胞的ｍｉｎ１值分别为６０７０±５１０及４２５０±５２０。当加入１０５ｍｏｌ／Ｌ维拉帕米、硝苯地平、恬而心时，其ｍｉｎ１值分别为３３３０±３７０和２７８０±１１０，４５８０±４２０和３０３０±３６０，４０００±４６０和３０９０±２８０（Ρ均＜００５）。而经ＰＤＧＦ、凝血酶刺激后，３ＨＵｒ、３ＨＬｅｕ掺入系膜细胞的ｍｉｎ１值在加入１０５ｍｏｌ／Ｌ维拉帕米、硝苯地平及恬而心前后差异不大（Ρ均＜００５）。结论：较高浓度的钙拮抗剂均能抑制由ＰＤＧＦ、凝血酶诱导的系膜细胞增殖，而对其肥大没有影响。其理论机理?OBJECTIVE Mesangial cell proliferation plays an important role in the pathogenesis of many glomerular diseases. In the mitogenic process of mesangial cells, Cytosolic free Ca 2+ is a critical intracellular signal which might be intervened with the use of calcium channel blockers. In the present study, the mitogen stimulated proliferation and hypertrophy of cultured mesangial cells were studied with the addition of verapamil, nifedipine and diltiazem. METHODOLOGY Cultured human mesangial cells of 4th to 6th passage were incubated with mitogens as PDGF and thrombin. Nifedipine, verapamil and diltiazem were applied to the stimulated mesangial cells and co cultured for 48 hours at 37℃ in 5% CO 2 in 96-well plastic plates. TdR(1μCi/well), Ur(1μCi/well), Leu(1μCi/well) was added to each well to incubate for another 24 hours. Then the cells were harvested and counted in scintillation fluid. RESULTS 3H TdR incorporations induced by PDGF and thrombin in mesangial cells were 6070±510/min and 4250±520/min. After 10 -5 mol/L verapamil, nifedipine and diltiazem were added, the 3H TdR incorporations induced by PDGF and thrombin were significantly decreased(3330±370 and 2780±110 for verapamil, 4580±420/min and 3030±360/min for nifedipine, 4000±460/min and 3090±280/min for diltiazem; P <0 05). The differences of 3H Ur and 3H Leu incorporation in mesangial cells induced by PDGF and thrombin were found to be of no significance( P >0 05) before and after the added of verapamil, nifedipine and diltiazem. CONCLUSION Calcium channel blockers as nifedipine, verapamil and diltiazem at high concentration can inhibit human mesangial cell proliferation induced by PDGF or thrombin in culture; while exert no effect on mesangial cell hypertrophy. These agents may be beneficial in preventing or attenuating renal diseases characterized by proliferation of mesangial cells.

关 键 词：钙拮抗剂 系膜细胞 增殖 

分 类 号：R392.12[医药卫生—免疫学]