肿瘤坏死因子相关的凋亡诱导配体对2型糖尿病大鼠内皮依赖性血管舒张功能的影响

Effects of tumour-necrosis-factor-related apoptosis-inducing ligand(TRAIL)on endothelium-dependent vasodilation function of aorta in type 2 diabetic rats

目的观察TNF相关的凋亡诱导配体(TRAIL)对T2DM大鼠主动脉内皮依赖性血管舒张功能的影响及其可能的机制。方法选取4周龄雄性SD大鼠,分为正常对照组(NC,n=10)与模型组(n=40),随机将模型组分为T2DM亚组(n=10)与TRAIL亚组(TRAIL,n=10)。TRAIL干预6周后,检测各组FPG及FIns水平,计算ISI。检测NC组与TRAIL亚组血清TRAIL水平。观察大鼠离体主动脉内皮依赖性血管舒张反应,并检测主动脉一氧化氮(NO)含量、内皮型一氧化氮合酶活性(eNOS)。结果与NC组比较,T2DM亚组FPG、FIns水平升高(P<0.01),ISI降低(P<0.01),血清TRAIL水平降低(P<0.01);血管内皮功能失调,乙酰胆碱(Ach)引起的血管最大舒张率降低(P<0.01),血管中NO含量及eNOS阳性表达降低(P<0.01或P<0.01)。TRAIL亚组血管Ach的舒张反应改善(P<0.01);血管中NO含量增加且eNOS阳性表达上调(P<0.05或P<0.01);FPG、FIns降低,ISI提高(P<0.01)。结论 TRAIL改善T2DM大鼠内皮依赖性血管舒张功能的同时,可促进具有血管保护作用的NO生成。

Objective To observe the effects of TRAIL on endothelium-dependent vasodilation function of aorta in type 2 diabetic rats and to investigate the mechanism involved.Methods Four-weekold male sprague dawley rats were rendered diabetic by intraperitoneal injections of STZ after high fat diet for 6 weeks.Diabetic rats were randomly divided into T2DM group and treatment （TRAIL） group,and normal rats were used as normal control （NC） group.For injection of recombinant TRAIL （rTRAIL）,rats received an intraperitoneal injection of rTRAII （20 μg/d） for 5 consecutive days.After 6 weeks,fasting plasma glucose,plasma insulin and serum TRAIL were measured respectively.Endothelial function was examined by acetylcholine-induced endothelium-dependent vasodilation using aortic rings.NO levels and eNOS activity were measured in isolaed aorta of rats.Results The FBG and FIns levels were significantly higher in T2DM group than in NC group （P ＜ 0.01）.The ISI level,serum TRAIL concentration,NO level and positive expression of eNOS was significantly lower in T2DM group than in NC group （P ＜0.01）.Concentration-dependent vaso-relaxation in response to Ach was significantly lower in T2DM group than in NC group [（63.5 ± 4.6）％ vs （93.5 ± 2.6） ％ relaxation at 10-4 mmol/L acetylcholine,P＜0.01].Recombinant TRAIL treatment significantly improved the vaso-relaxation response to Ach [（78.4±2.7）％ vs （63.5±4.6）％ at 10 4 mmol/L,P＜0.01],increased ISI level,NO concentration and positive expression of eNOS （P＜0.01）,and reduced the FPG,FIns levels （P＜0.01）.Conclusion TRAIL improves endothelium-dependent vasodilation function by enhancing NO synthesis and eNOS activity.