雷帕霉素对高糖诱导的大鼠肾系膜细胞增殖、凋亡和细胞周期的影响

目的:评价雷帕霉素对高糖诱导的肾系膜细胞增殖、凋亡和细胞周期的影响,探讨其在糖尿病肾病防治中的意义。方法:体外培养的大鼠肾小球系膜细胞株HBZY-1 分为:正常对照组、高糖组、高糖加不同浓度的雷帕霉素组,应用CCK-8 法观察细胞增殖的变化;流式细胞术检测各组细胞的细胞周期和凋亡情况;Real-time PCR 法检测各组细胞中血管紧张素 (ANG )、转化生长因子β1(TGF-β1)和血管内皮生长因子(VEGF)的表达水平。结果:高糖诱导下HBZY-1 的增殖水平明显上升,凋亡水平下降,ANG ,TGF-β1 和VEGF 的表达水平上升,而雷帕霉素具有明显抑制作用,且有剂量依赖性,并下调ANG ,TGF-β1 和VEGF 的表达;对于细胞周期,高糖组的S 期细胞明显高于正常组(P<0.05);雷帕霉素干预后,S 期细胞比例减少(P<0.05)。结论:雷帕霉素能够抑制高糖状态下HBZY-1 的增殖,促进其凋亡及导致G1/ S 期阻滞,同时下调ANG ,TGF-1β和VEGF 的表达。

Effect of rapamycin on proliferation,apoptosis and cell cycles of high glucose-cultured rat glomerular mesangial cell

Objective:To evaluate the effects of rapamycin on the proliferation,apoptosis and cell cycle of glomerular mesangial cells induced by high glucose,and to explore its significance in the prevention and treatment of diabetic nephropathy.Methods: The rat GMC HBZY-1 was divided into four groups:control group,high glucose group,the first group of high glucose plus rapamycin,the second group of high glucose plus rapamycin.CCK-8 assay was used to detect the proliferation of cells,flow cytometry was introduced to evaluate the apoptosis and cell cycle of HBZY-1,Real-time PCR was used to detect the mRNA of Angiotensin (ANG ),transforming growth factor beta1(TGF 1) and vascular endothelial growth factor (VEGF).Results: The proliferation level of HBZY-1 induced by high glucose was significantly increased,and the level of apoptosis decreased,and the expression level of ANG ,TGF-1and VEGF was increased.Rapamycin significantly inhibited,and there was a dose dependent,and down regulated the expression of ANG,TGF-1,and VEGF.For the cell cycle,the S phase cells in the high glucose group were significantly higher than those in the normal group (P<0.05),and the S phase cell proportion was decreased after rapamycin intervention (P<0.05).Conclusion: Rapamycin can inhibit the proliferation of HBZY-1 in high glucose,promote its apoptosis and lead to G1/ S arrest,and down regulate the expression ofANG ,TGF-1 and VEGF.