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目的探讨辛伐他汀诱导高糖培养下肾小球系膜细胞凋亡是否与上调第二线粒体源半胱天冬氨酸蛋白酶激活物(Smac)表达有关。方法用不同浓度辛伐他汀刺激高糖培养下的系膜细胞,采用Hoechst 33258荧光染色观察细胞凋亡形态,碘化丙啶染色(PI)、流式细胞术(FCM)定性及定量检测细胞凋亡率,免疫荧光法观察Smac蛋白表达。结果高糖+辛伐他汀组与高糖组相比,12、24、48 h细胞凋亡荧光强度、细胞凋亡率、免疫荧光示Smac蛋白表达均明显增加(P<0.05),且均呈时间、浓度依赖性;各组相应时间段内Smac荧光强度与细胞凋亡荧光强度间呈正相关(r=0.9353,P<0.05)。结论高糖环境下辛伐他汀能通过上调Smac蛋白表达抑制系膜细胞增殖、诱导系膜细胞凋亡;其作用呈浓度和时间依赖性。
Objective To investigate whether simvastatin can induce mesangial cell apoptosis under high glucose conditions and upregulate the expression of the second mitochondrial caspase (Smac). Methods Different concentrations of simvastatin were used to stimulate mesangial cells cultured in high glucose. Hoechst 33258 fluorescence staining was used to observe the morphology of apoptotic cells. Propidium iodide (PI) and flow cytometry (FCM) Mortality and immunofluorescence were used to observe Smac protein expression. Results Compared with high glucose group, the apoptotic fluorescence intensity, apoptosis rate and immunofluorescence of Smac protein expression in high glucose + simvastatin group were significantly increased (P <0.05) at 12, 24 and 48 h Time and concentration. There was a positive correlation between the fluorescence intensity of Smac and the fluorescence intensity of apoptosis (r = 0.9353, P <0.05). Conclusion Simvastatin can induce mesangial cell apoptosis by up-regulating the expression of Smac protein in high glucose environment in a concentration-and time-dependent manner.