内毒素血症大鼠胰岛β-细胞功能损害的研究

Study of Dysfunction of Insulin Secretion in Islet β-Cells During Endoxemia in Rats

目的 探讨内毒素对大鼠胰岛 β 细胞胰岛素分泌功能的作用机理。 方法 以腹腔注射脂多糖 (LPS ,2mg kg体重 )制成大鼠内毒素血症模型 ,观察其血浆葡萄糖、胰岛素及胰腺组织胰岛素含量的动态变化和胰岛细胞诱生型一氧化氮合酶 (iNOS)mRNA的表达情况 ,分析外源性NO对胰岛 β 细胞胰岛素合成和分泌的影响。结果 注射LPS后 12h ,大鼠血中葡萄糖浓度明显升高 ,1d达峰值并持续到 3d后。血中胰岛素水平 6h明显升高并持续到 3d后 ,而胰腺组织中的胰岛素水平变化不明显。胰岛 β 细胞iNOSmRNA表达亦于注射LPS 6h后明显增强 ,并出现DNA损伤的慧星尾。外源性NO严重抑制葡萄糖刺激胰岛 β 细胞合成与分泌胰岛素。结论 内毒素通过刺激存在于胰岛的炎症细胞和非炎症细胞 (β 细胞 )iNOS的表达 ,诱导NO的产生 ,选择性造成胰岛 β 细胞的损伤和抑制胰岛素的合成与分泌 ;同时内毒素血症还可以通过另外的途径促进胰岛素分泌引起高胰岛素血症 ,最终导致胰岛 β 细胞功能紊乱 (衰竭 )和胰岛素抵抗。

Objective To explore the effect of endotoxin on insulin secretion from islet β cell of rat pancreas.Methods After the model of endotoxemia was established in rats with intraperitoneal injection of LPS (2 mg/kg),the changes of insulin level in the serum and pancreas were dynamically determined, the expression of inducible nitric oxide synthase (iNOS) by situ hybridization and DNA damage in islet cells were also observed, the effect of sodium nitroprusside (exogenous NO) on synthesis and secretion of insulin from isolated islet β cell of normal rat pancreas under high glucose stimulation was also evaluated.Results The level of glucose and insulin in plasma were significantly increased at 12th and 6th h, respectively and kept on 3 d after injection of LPS,but the insulin level in pancreas was not remarkably altered.The expression of iNOS and DNA damaged significantly enhanced at 6 d after endotoxemia. The high glucose stimulated insulin synthesis and secretion were strongly inhibited by exogenous NO.Conclusion These findings suggest that LPS be stimulate the expression of iNOS and NO product,which inhibites synthesis and secretion of insulin in islet β cells,but it stimulates insulin secretion by another mechanism,and results in dysfunction and destruction of the rat pancreas.