内毒素对大鼠胰岛细胞凋亡及其意义的研究

Studies on the effets of endotoxin on apoptosis of rat pancreatic islet cells and their significance

目的 探讨内毒素对大鼠胰岛细胞凋亡作用的意义。方法 采用单细胞凝胶电泳和DNA凝胶电泳技术 ,分析外源NO供体 (硝普钠 )和LPS对离体胰岛细胞的凋亡及胰岛素合成与分泌的影响。结果 体外试验显示 ,外源NO明显引起胰岛细胞DNA断裂 ,出现慧星尾和凋亡梯状带 ,并呈剂量依赖关系。高浓度NO(6 0mmol/LSNP)可引起胰岛细胞DNA随机降解。外源NO强烈抑制葡萄糖刺激 β 细胞的胰岛素合成与分泌。LPS离体条件下 ,对胰岛细胞凋亡作用不明显。 结论 LPS通过整体作用诱导炎症细胞和胰岛细胞iNOS表达 ,产生NO介导胰岛细胞凋亡 。

Objective To explore the significance of the effects of endotoxin (LPS) on apoptosis of pancreatic islet cells in rats.Methods DNA damage of islet β cells in rats by the extermal donor of NO(sodium nirtoprusside)and LPS in vitro with single cell gel electrophoresis and DNA agarose gel electrophresis were observed ,the synthesis and secredtion of insulin under high glucose stimulation were also evaluated.Results In vitro experiment showed that exogenous NO markedly cause the damage of DNA and strongly inhibited the high glucose stimulated insulin synthesis and secretion in islet β cells, but LPS did not exert the same effect.Conclusion The mechanism of the effcts of endotoxin on apoptosis of islet β cells might be stimulating the expression of iNOS in inflammatory or non inflammatory risident islet cells that generates the NO inducing the DNA damage and the dysfunction of islet cells.