钾通道阻断剂四乙胺对胰岛β细胞凋亡的作用机制研究  

Effect of tetraethylammonium on the apoptosis of pancreatic β cell

作　　者：虞涛[1] 陈群力[2] 胡萍[1] 邵静芳[1] 杨敬[1] 沈关心[1] 

机构地区：[1]华中科技大学同济医学院免疫学系 [2]河南科技大学生物化学教研室

出　　处：《中国糖尿病杂志》2006年第4期284-287,共4页Chinese Journal of Diabetes

基　　金：国家重点基础研究发展规划(973)资助项目(CB510008);国家自然科学基金资助项目(30300166)

摘　　要：目的研究钾通道阻断剂四乙铵(TEA)对诱导胰岛β细胞凋亡的作用及机制。方法以STZ诱导小鼠胰岛细胞株(NIT)细胞凋亡,同时加入TEA,通过AnnexinV检测、PI染色、Rho-damine123染色,使用流式细胞术检测TEA对NIT细胞凋亡的影响;测定培养上清中NO和氧自由基含量,以及细胞裂解物中过氧化物歧化酶(SOD)活性。结果STZ可显著诱导NIT细胞凋亡,并可降低SOD的活性,显著增加培养上清中氧自由基及NO的含量;1mmol/LTEA能显著抑制STZ的作用。结论钾通道在胰岛β细胞的凋亡中可能起重要作用;TEA可显著抑制STZ诱导的胰岛β细胞凋亡,其机制可能与上调NIT细胞SOD活性,增强其清除氧自由基的能力及减少NO的产生有关。Objective To examine the effect of tetraethylammonium （TEA, K^＋ channel blocker） on pancreatic β-cell apoptosis and explore the mechanism. Methods Mouse β cells （NIT cells） were exposed to streptozotocin（STZ） to induce apoptosis, and TEA of different concentrations were applied along with STZ to prevent efflux of intracellular K^＋. Cells were stained with annexin V, PI and rbodamine 123. Flow cytometer （FCM） was used to determine the percent of apoptotic or viable cells and the change of mitochondrial membrane potential. Culture media was collected to quantify the content of NO and ROS produced by NIT-cells. Cells were collected for detecting the activity of super oxide dismutase （SOD） in cells lysates. Results STZ induced apoptosis of NIT cells significantly （P〈0.01） and 1 mmol/L TEA inhibited the effect of STZ （P〈0.01）. Productions of ROS （P〈0.01） and NO （P〈0.01） in NIT cells treated with STZ were reduced by TEA significantly. Activity of SOD in cytoplasm of NIT cells was down-regulated by STZ（P〈0.01） significantly. Conclusions K~ channel may play an important role in apoptosis of pancreatic β cells. K^＋ channel blocker TEA may inhibit the apoptosis of pancreatic β cells significantly, which may correlate the down-regulating activity of SOD and the reducing of production of ROS and NO.

关 键 词：胰岛Β细胞 钾通道阻滞剂 细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]