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咪唑立宾对大鼠肾小球系膜细胞增殖的抑制作用

ISSN号：1001-7097
期刊名称：《中华肾脏病杂志》
时间：0
分类：R692.6[医药卫生—泌尿科学;医药卫生—临床医学;医药卫生—外科学]
作者机构：[1]解放军总医院全军肾脏病研究所暨肾脏病重点实验室,北京100853
相关基金：国家自然科学基金创新研究群体基金（30121005）、重点项目（30630033）和面上项目（30570856）

作者：刘书馨[1], 谢院生[1], 陈香美[1], 吕杨[1], 傅博[1], 尹忠[1], 洪权[1]

关键词：细胞周期, 细胞周期调节蛋白, 咪唑立宾, 系膜细胞, Cell cycle, Cell cycle-regulatory proteins, Mizoribine, Mesangial cell

中文摘要：

目的探讨咪唑立宾（MZ）对肾小球系膜细胞增殖的抑制作用及其对细胞周期蛋白依赖性蛋白激酶抑制物p27^kip1表达的影响。方法大鼠系膜细胞同步后分为无血清组、20％FCS刺激组、20％FCS＋MZ组。四甲基偶氮唑盐（MTT）法检测细胞数。BrdU标记法检测S期细胞。流式细胞仪检测细胞周期。Western印迹检测p27^kip1蛋白的表达。结果MZ可抑制20％FCS刺激所致的系膜细胞增殖，呈剂量依赖性。与20％FCS刺激组比较，20％FCS＋MZ组S期细胞的百分比显著降低[（10．28±1．26）％比（21．04±5．38）％，P〈0．05]。MZ可改善由20％FCS刺激诱导的GO／G1期细胞减少[（83．53±2．50）％比（71．15±1．25）％]和S期细胞增加[（12．22±1．22）％比（23．19±0．38）％，P〈0．051。20％FCS刺激后p27^kip1蛋白表达显著下降，MZ上调p27^kip1蛋白表达。结论MZ能够有效抑制系膜细胞增殖，作用时相在G1／S期转化，其抑制系膜细胞增殖的作用部分是通过上调p27^kip1蛋白表达实现的。

英文摘要：

Objective To explore the inhibitory effect of mizoribine（MZ） on rat mesangial cell proliferation and its influence on CKI p27^kip1 expression in vitro. Methods Primary cultured rat mesangial cells were divided into 24 hr FCS free group, 20% FCS group, and 20% FCS＋MZ （0.5-50 mg/L）group. Cell numbers were detected by MTT. S phase entry was measured by BrdU labeling. Cell cycle profiles were determined by flow cytometric analysis. The expression of p27^kip1 protein was detected by Western blotting. Results MZ inhibited FCS-stimulated mesangial cell proliferation in a dose-dependent manner. Cell cycle analysis and BrdU labeling showed that MZ prevented FCS-stimulated mesangial cells from entering S phase [（12.22±1.22）% vs （23.19±0.38）%, P〈0.05]. The expression of p27^kip1 protein was down-regulated by FCS, which was significantly counteracted by MZ. Conclusion MZ can inhibit mesangial cell proliferation effectively in vitro, which is at least partly mediated through up-regulating the expression of p27^kip1 protein.

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