·糖尿病基础研究·

　　【摘要】目的 观察肿瘤坏死因子(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(NC，n=10)组,T2DM亚组(n=10)与TRAIL干预(TRAIL,n=10)亚组。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亚组大鼠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)，血管组织中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);血管组织中NO含量增加且eNOS阳性表达上调(P<0.01;P<0.01);降低FPG、FIns，提高ISI(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。

　　【关键词】肿瘤坏死因子相关的凋亡诱导配体;糖尿病，2型;血管功能;一氧化氮;大鼠

　　【Abstract】Objective To observe the effects of TNF-related apoptosis-inducing ligand(TRAIL) on endothelium-dependent vasodilation function of aorta in T2DM rats and to investigate the mechanism. Methods Four-week-old male sprague dawley rats were establishedT2DM model by intraperitoneal injections ofSTZ after high fat diet for 6 weeks. Diabetic rats were randomly divided into T2DM subgroup and TRAIL intervention (TRAIL) subgroup, and normal rats were enrolled as normal control (NC) group(n=10,in each). Intraperitoneal injection of TRAIL (20μg/day) in TRAIL group for 5 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. Result Compared with NC group, the FBG, FIns levels were significantly higherin T2DM group(P<0.01). The levels of ISI, NO, serum TRAIL concentrationandpositive expression of eNOSwere significantly lower inT2DM groupthan in NC group(P<0.01).Concentration-dependent vasorelaxation in response to Achwas significantly decreased in T2DM group versus NC group[(93.5±2.6)% vs (63.5±4.6)%, relaxation at 10-4mmol/L acetylcholine, P<0.01)]. Recombinant TRAIL treatment improvedthevasorelaxationresponse toAch[(78.4±2.7)% vs (63.5±4.6)% at 10-4mmol/L Ach, P<0.01], increased ISI level, NO concentration andpositive expressionof eNOS (P<0.01), and reduced the levels of FBG, FIns(P<0.01).ConclusionTRAIL improves endothelium-dependent vasodilation function by enhancing NO synthesis and eNOS activity.

　　【Key words】 TNF-related apoptosis-inducing ligand(TRAIL);Diabetes mellitus, type 2;Vascular endothelial function;Nitric oxide; Rats