·糖尿病基础研究·

　　廖洁 雷闽湘 陈雄 胡维 王爱民

　　作者单位：410008长沙，中南大学湘雅医院干部医疗科(廖洁、陈雄)，内分泌科(雷闽湘、胡维)，急诊科(王爱民)

　　通讯作者：雷闽湘， E-mail:lmx618@medmail.com.cn

　　【摘要】目的观察比较血糖波动对糖尿病大鼠血管内皮依赖舒张功能的影响及其初步机制。方法60只SD大鼠随机分成正常组、持续组和血糖波动组。血糖波动组每日2次皮下注射胰岛素的方法诱导血糖波动。干预12周后处死大鼠，取各组大鼠主动脉测离体舒张功能、NO浓度及Western blot方法检测PI3K、蛋白激酶B(PKB/Akt)、内皮型一氧化氮合酶(eNOS)蛋白表达水平。结果波动组和持续组大鼠胸主动脉内皮依赖性血管舒张功能低于正常组(P<0.01)，波动组又明显低于持续组(P<0.05);波动组及持续高血糖组的NO浓度、PI3K及磷酸化Akt、eNOS蛋白表达水平均较正常组显著下调(P<0.01)，而波动组又显著低于持续组(P<0.05)。结论长期血糖波动可以明显引起糖尿病大鼠血管内皮依赖性舒张功能下降，可能与抑制PI3K/Akt/eNOS信号通路活化所导致NO的产生降低有关。

　　【关键词】血糖波动;血管内皮舒张功能;一氧化氮

　　doi:10.3969/j.issn.1006-6187.2012.02.018

　　Effects of a high blood glucose fluctuation on endothelium-dependent vasodilation function in diabetic ratsLIAO Jie, LEI Min-xiang, CHEN Xiong, et al. Central-South University Xiangya Hospital, Chansha 410008, China

　　Corresponding author: LEI Min-xiang, E-mail:lmx618@medmail.com.cn

　　【Abstract】ObjectiveTo investigate the effects of a blood glucose fluctuation on endothelium-dependent vasodilation function in diabetic rats. MethodThe 60 SD rats were assigened into normal control group, sustained high blood glucose group and blood glucose fluctuation group. Blood glucose fluctuations were induced by insulin subcutaneous injection twice daily. Three months after intervention, aorta was extracted for endothelium - dependent vasodilation function measurement, and NO was measured by Griess reaction. The protein of PI3K, Akt and eNOS were measured by Western blot. ResultAn endothelium-dependent vasodilation function and NO production were significantly decreased in high blood glucose fluctuation group versus sustained high blood glucose group(P<0.05). PI3K-P85, phosphorylation of eNOS-Serl177 and Akt-Ser473 in intermittent high glucose group were significantly lower than in constant high glucose group(P<0.05)ConclusionThese findings suggest that variability in glycemic control could attenuated endothelium-dependent vasodilation function by inhibiting PI3K/Akt/eNOS pathway.

　　【Key words】Glucose fluctuation; Endothelium-dependent vasodilation function; Nitric oxdie