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雷诺嗪对高脂高糖诱导的胰岛β细胞NIT-1功能损伤的保护作用

Effect of Ranolazine on the Dysfunction of NIT-1 Cell Induced by High Glucose and Saturated Fatty Acids

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【作者】 张洁徐西振李瑞李影马奔

【Author】 ZHANG Jie,XU Xi-zhen,LI Rui,LI Ying,MA Ben(Department of Internal Medicine and the Institute of Hypertension,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

【机构】 华中科技大学同济医学院附属同济医院高血压病研究所

【摘要】 目的观察雷诺嗪对高糖高脂诱导的胰岛β细胞NIT-1三酰甘油(TG)含量及脂肪酸转位酶(FAT/CD36)表达的增加和胰岛素分泌功能损伤的保护作用。方法用放免法检测高糖高脂及5μmol.L-1雷诺嗪共同作用后细胞基础胰岛素分泌(BIS)和葡萄糖刺激后胰岛素分泌(GSIS)水平的变化,酶法检测胞内TG含量,Western blot检测细胞FAT/CD36蛋白的表达。结果正常组、高糖高脂组和雷诺嗪组的胞内TG含量分别为(2.31±0.05),(5.17±0.03)和(3.63±0.01)mmol.L-1;BIS分别为(0.67±0.03),(0.32±0.07),(0.51±0.03)ng.mL-1,GSIS分别为(1.68±0.17),(1.35±0.08),(1.47±0.11)ng.mL-1;FAT/CD36的相对表达量比值A1分别为(0.53±0.08),(1.78±0.05)和(1.07±0.06)。与正常组比较,高糖高脂组GSIS降低,细胞内TG含量增多。FAT/CD36蛋白表达显著增加(P<0.05)。而雷诺嗪与高糖高脂的共同作用24 h后可以显著升高GSIS,同时降低胞内TG含量,减少FAT/CD36蛋白。结论雷诺嗪对高糖高脂导致的胰岛细胞NIT-1分泌功能损伤有保护作用,同时可以减少胞内脂质沉积,其分子机制可能是通过脂肪酸转位酶FAT/CD36蛋白表达的改变。

【Abstract】 Objective To study the effect of ranolazine on the contents of triglyeride(TG),fatty acid translocase(FAT)/CD36 and insulin secretion in insulinoma cell line NIT-1 induced by high glucose and saturated fatty acid.Methods NIT-1 cells were cultured with high glucose,saturated fatty acid together and 5 μmol·L-1 ranolazine.Radioimmunoasssay method was used to detect cell basic insulin secretion(BIS) and glucose-stimulating insulin secretion(GSIS).TG in the cells was detected by enzyme assay and FAT/CD36 protein expression was determined by Western blot.Results In normal,high glucose and saturated fatty acid treatment and ranolazine treatment groups,the TG content was(2.31±0.05),(5.17±0.03) and(3.63±0.01) mmol·L-1,respectively.BIS in each group was(0.67±0.03),(0.32±0.07),(0.51±0.03) ng·mL-1;GSIS of each group was(1.68±0.17),(1.35±0.08),(1.47±0.11) ng·mL-1;FAT/CD36 relative expression ratio A1 in each group was(0.53±0.08),(1.78±0.05) and(1.07±0.06).As compared with the normal control,high glucose and saturated fatty acid could decrease the GSIS and increase the TG content and significantly increase the FAT/CD36 protein expression(P<0.05).But after co-treatment of high glucose,saturated fatty acid and ranolazine for 24 h,the GSIS was increased significantly,at the same time the intra-cellular TG content and the FAT/CD36 protein expression was decreased.Conclusion Ranolazine can protect the secretion function of NIT-1 cells impaired by high glucose and saturated fatty acid,and decrease TG content in the cells probably through the change of FAT/CD36 protein expression.

【基金】 国家自然科学基金资助项目(81000047)
  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2012年04期
  • 【分类号】R965
  • 【下载频次】88
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