急性糖负荷对正常大鼠血管功能的影响

摘要

目的 探讨急性糖负荷对正常大鼠血管功能的影响及机制.方法 取Wistar大鼠(n=5)的胸主动脉进行离体血管功能测定.血管环在含不同浓度葡萄糖(25、50、100 mmol/L)的高糖溶液(高糖组)和含不同浓度甘露醇(25、50、100 mmol/L)的高渗溶液(高渗对照组)中分别孵育10 min,设立空白对照组.运用张力换能器测定各组血管对苯肾上腺素(PE)的收缩反应及对乙酰胆碱(Ach)的舒张反应,分别采用DCF法和DAF-FM荧光探针检测血管环活性氧(ROS)和一氧化氮(NO)的相对生成量.结果 空白对照组、高糖组和高渗对照组血管对1 μmol/L PE诱导的收缩反应比较差异无统计学意义(P＜0.05)；与空白对照组比较,高糖组和高渗对照组对1 μmol/L Ach诱导的舒张反应随葡萄糖浓度和渗透压的升高呈逐渐减弱趋势(P＜0.05),且高渗对照组舒张反应的减弱程度较高糖组更为显著(P＜0.05).高糖组和高渗对照组血管环NO相对生成量以及高糖组ROS相对生成量均显著高于空白对照组(P＜0.05或P＜0.01),高渗对照组ROS相对生成量与空白对照组比较差异无统计学意义(P＞0.05).结论 急性糖负荷可使血管舒张功能减弱,并呈现一定的浓度依赖性,可能与ROS生成量增加造成内皮功能损伤有关；高渗透压导致NO生成过多也可能作为自由基损伤血管.%Objective To investigate the influence and possible mechanism of acute hyperglycemia on vessel function of normal rats. Methods The isolated thoracic aorta of Wistar rats ( n = 5) were taken for determination of vascular function in vitro. Vascular rings were incubated with high glucose solution containing 25, 50 and 100 mmol/L glucose (high glucose group) or hyperosmotic solution containing 25, 50 and 100 mmol/L mannitol ( hyperosmotic control group) for 10 min, and blank control group was also established. The contraction response to phenylephrine ( PE) and relaxation response to acetylcholine (Ach) of vessels were examined with tension transducer, and the relative production of reactive oxygen species (ROS) and nitric oxide (NO) of vascular rings was determined with DCF method and DAF-FM fluorescent probe respectively. Results There was no significant difference in the contraction response to 1 μmol/L PE among blank control group, high glucose group and hyperosmotic control group (P >0. 05). Compared with blank control group, the relaxation response to 1 μmol/L acetylcholine in high glucose group and hyperosmotic control group decreased with the increase of glucose concentrations and osmotic pressure (P <0. 05), and the decrease of relaxation response in hyperosmotic control group was more significant than that in high glucose group (P <0.05). The relative production of NO in high glucose group and hyperosmotic control group and the relative production of ROS in high glucose group were significantly higher than thosein blank control group (P < 0. 05 or P < 0.01), while there was no significant difference in the relative production of ROS between hyperosmotic control group and blank control group ( P > 0. 05). Conclusion Acute high glucose leads to concentration-dependent reduction in vasodilatation, which may be associated with the endothelial damage caused by increased ROS production. Excessive NO production induced by hyperosmosis may also serve as free radicles to damage blood vessels.