中文摘要：

目的：观察辛伐他汀对小鼠胰腺B细胞株MIN6胰岛素分泌功能的影响并探讨其可能机制。方法：将MIN6细胞随机分为正常对照组和低、中、高浓度辛伐他汀组，分别用含0、2、5、10μmol／L辛伐他汀和15％胎牛血清的高糖DMEM培养基培养48h。采用放射免疫分析法检测辛伐他汀对MIN6细胞胰岛素分泌功能的影响；生物化学发光法测定细胞内ATP含量；用实时荧光定量PCR检测内向整流钾离子通道6．2（Kit6．2）、电压依赖性钙离子通道1．2（Ca，1．2）及葡萄糖转运体2（GLUT2）mRNA表达水平；用Western印迹检测Kir6．2、Ca，1．2及GLUT2蛋白表达水平。结果：5和10μmol／L的辛伐他汀能够明显减少MIN6细胞胰岛素的合成及分泌（P〈0．05）；辛伐他汀处理组MIN6细胞内ATP水平较正常对照组明显降低（P〈0．05）；辛伐他汀各处理组MIN6细胞Kir6．2mRNA表达水平较正常对照组明显上调（均P〈0．01），5和10μmol／L辛伐他汀组Ca。1．2mRNA水平明显下调（均P〈0．01），GLUT2mRNA表达水平明显下调（P〈0．05）；5和10μmol／L辛伐他汀处理组Kir6．2蛋白表达较正常对照组明显升高（均P〈0．01），10μmol／L辛伐他汀处理组Cav1．2及GLUT2蛋白表达水平明显下降（均P〈0．01），5μmol／L辛伐他汀组Cav 1．2蛋白表达水平较正常对照组亦有明显下降（P〈0．01）。结论：辛伐他汀对小鼠胰腺B细胞株MIN6胰岛素的合成和分泌具有一定的抑制作用。辛伐他汀可能通过抑制MIN6细胞内ATP的生成以及上调MIN6细胞Kil6．2、下调Cav1．2和GLUT2的表达从而影响其胰岛素的合成和分泌。

英文摘要：

AIM： To observe the influence of simvastatin on insulin secretion function of mouse pancreatic beta cell line MIN6 and to explore its possible mechanisms. METHODS： MIN6 cells were randomly divided into normal control group and low-, middle-and high-concentration simvastatin treatment groups, which were cultured for 48 h with high-glucose DMEM containing 15% fetal bovine serum plus 0, 2, 5 and 10 μmol/L simvastatin, respectively. The insulin secretion of MIN6 ceils was measured by radioimmunoassay. The content of ATP in MIN6 cells was measured by biochemiluminescence method. The mRNA and protein expression levels of inwardly rectifying potassium channel 6.2 （ Kir6, 2）, voltage-dependent calcium channel 1.2 （ Cav 1.2） and glucose transporter 2 （GLUT2） were detected by real-time fluorescence quantitative PCR and Western blotting, respectively. RESULTS： Compared with normal.control group, middle-and high-concentration simvastatin treatment markedly decreased the synthesis and secretion of insulin m MIN6 cells （P 〈 0.05）. The content of ATP in MIN6 cells was markedly decreased in simvastatin treatment groups （ P 〈 0. 05）. The mRNA expression level of Kit6.2 in MIN6 cells was significantly up-regulated in simvastatin treatment groups （ P 〈 0. 01 ）, while the mRNA expression levels of Cav 1.2 and GLUT2 were significantly down-regulated in middle-and high-concentration simvastatin treatment groups （ P 〈 0. 01 ）.the protein expression of Kit6.2 was significantly increased but that of Cavl. 2 was significantly decreased in middle-and high-concentration simvastatin treatment groups （P 〈 0. 01 ）, and the protein expression level of GLUT2 was markedly decreased in high-concentration simvastatin treatment group （P 〈 0. 01 ）.CONCLUSION： Simvastatin inhibits insulin synthesis and secretion in mouse pancreatic beta cell line MIN6 via suppress- ing ATP production, up-regulating the expression of Kir6.2 and down-regulating the expression of Cav 1,2 and GLUT2. [