辛伐他汀对小鼠胰岛β细胞三磷酸腺苷敏感性钾通道和L型钙通道的影响

Effect of Simvastatin on ATP-sensitive K＋ channels and L-type Ca2＋ channels in mouse pancreatic beta cells

目的 观察辛伐他汀对小鼠胰岛β细胞株MIN6 三磷酸腺苷敏感性钾通道（KATP）和L型钙通道（L-Ca）电流的影响. 方法 将MIN6细胞分0.05％二甲基亚砜（DMSO）组、正常对照组和低、中、高浓度辛伐他汀组,分别用含0.05％ DMSO和含0、2、5、10 μmol/L辛伐他汀浓度的15％胎牛血清高糖DMEM培养基培养48 h.采用全细胞膜片钳技术记录细胞KATP和L-Ca电流. 结果 MIN6细胞正常细胞外液灌流时KATP最大电流密度为（92.81±4.10） pA/pF,用含2、5及10μmol/L浓度辛伐他汀培养基培养48 h后细胞钾电流增加,分别为（117.94±3.67） pA/pF、（153.91±12.38） pA/pF、（307.01±6.40） pA/pF（均P＜0.01）.MIN6细胞高糖细胞外液灌流时LCa最大电流密度为（-21.03±0.55）pA/pF,3种浓度辛伐他汀培养基干预后的电流密度分别降至（-16.31±0.51） pA/pF、（-10.75±0.71）pA/pF、（3.30±0.46） pA/pF（均P＜0.01）. 结论 辛伐他汀对小鼠胰岛β细胞株MIN6细胞KATP电流具有增大作用,对L-Ca电流有减小作用,从而影响胰岛素的分泌,从而影响糖代谢.

Objective To observe the influence of Simvastatin on the ATP-sensitive K＋Channels and L-type Ca2＋ Channels in mouse pancreatic beta cell line MIN6.Methods MIN6 cells were divided into 0.05 % dimethyl sulfoxide （DMSO） group,normal control group and low-,middle-,high-concentration of Simvastatin treatment groups,that were cultured for 48 h with high-glucose DMEM containing 15% fetal bovine serum plus 0.05% dimethyl sulfoxide,0,2,5 and 10 μmol/Lsimvastatin,respectively.Whole-cell patch-clamp technology was used to record the currents of ATP-sensitive K＋ channels and L-type Ca2＋ channels in MIN6 cells.Results The mean potassium current density in normal external solution perfusion group was （92.81 ±4.10） pA/pF.Compared with normal external solution perfusion control group,2,5 and 10 μmol/L Simvastatin treatments markedly enhanced the current density of ATP-sensitive K＋ Channels,reaching to （117.94 ± 3.67）pA/pF,（153.91±12.38） pA/pF,（307.01±6.40） pA/pF （all P〈0.01）,respectively.The current density in L-type Ca2＋ Channels was （-21.03 ± 0.55） pA/pF in glucose external solution group.Compared with glucose external solution group,the current density in 2,5 and 10 μmol/L Simvastatin treatment groups were decreased to （16.31±0.51） pA/pF,（-10.75±0.71） pA/pF,（-3.30±0.46） pA/pF （all P〈0.01）,respectively.Conclusions Simvastatin inhibits insulin secretion and glycometabolism in mouse pancreatic beta cell line MIN6 via enhancing the current density of ATP-sensitive K＋ Channels and inhibiting the current density of L-type Ca2＋ Channels.