TFP5保护高糖诱发的胰岛β细胞损伤  

Protection effect of TFP5 on pancreatic cells from apoptosis induced high glucose through inhibition hyperactivity of Cdk5 induced by high glucose

作　　者：张霞 张彬[2] 郑亚莉 李博 郭江涛 曹旭芹 

机构地区：[1]宁夏人民医院肾脏内科,宁夏银川750002 [2]宁夏医科大学,宁夏银川750004

出　　处：《宁夏医学杂志》2014年第3期195-197,共3页Ningxia Medical Journal

基　　金：国家自然科学基金资助项目(81060066);宁夏自然科学基金资助项目(NZ10162);宁夏科技攻关资助项目(KGX-19-10-16);宁夏科技攻关国际合作项目资助项目(2011ZYH169)

摘　　要：目的探讨TFP5对高糖诱发的周期素依赖性蛋白激酶-5(Cdk5)过度活性的抑制作用及其对胰岛β细胞的保护作用。方法体外培养小鼠胰岛细胞株Min6,将TFP5转染到Min6细胞,空病毒载体为对照,比较转染率,并测定Cdk5激酶活性。将细胞分为低糖组(5 mmol·L-1)、高糖组(25mmol·L-1)和高糖+TFP5组,观察3组细胞中Cdk5激酶活性,并通过检测细胞凋亡标记Bax/Bcl-2评估细胞存活情况。结果 TFP5可有效转导进入Min6细胞内;高糖可诱导Cdk5过度活性,TFP5抑制高糖诱导的Cdk5过度活性;高糖刺激下Min 6细胞的Bax表达增加,Bcl-2表达减少,Bax/Bcl-2升高,细胞凋亡增加,而加入TFP5后可以减低Bax/Bcl-2的比值,减少细胞的凋亡。结论 TFP5可抑制高糖诱发的Cdk5激酶的过度活性、减少高糖刺激下胰岛细胞凋亡,具有潜在的以Cdk5为靶点治疗2型糖尿病的前景。Objective To explore the effect of TFP5 on hyper activation of Cdk5 and its impact on the survival pancreatic β cells. Methods Mouse insulinoma line6 （ Min6） cells were cultured in vitro. The TFP5 gene was delivered into Min6 cells to observe its expression and the activity of CdkS. Then we grouped the cells as following three groups： low glucose group （5mml/L）, high glucose group （25mmol/L） ,high glucose ＋ TFP5 group,and the activity of Cdk5 was detected from these cells and analyzed the cell survival by the expression of Bax and Bcl - 2 which examined by using Western Blot. Results TFP5 effectively penetrated cell membranes into the cells. High glucose induced the hyperactivity of CdkS, but TFP5 inhibited this course. High glucose led Min6 cells to express higher levelof Bax and lower level of Bcl -2, thus inducing cell apoptosis. TFP5, however,weakened this process, and protected Min6 cells from ap- optosis. Conclusion TFP5 inhibits the over activation of Cdk5, and protects pancreatic 13cells from apoptosis. It may be a potential ther- apeutic drug for type 2 diabetes targeted on Cdk5.

关 键 词：TFP5 周期素依赖性蛋白激酶5 葡萄糖 胰岛素 细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]