孕期糖尿病对子代大鼠血管内皮功能的影响及机制  

Effects of maternal diabetes on vascular endothelium functions and the possible mechanisms in rat male offspring

作　　者：陈硕[1,2] 王甲良[1,2] 罗浩[2] 王新全[2] 邹雪[2] 廖翔[2] 张苗[2] 贺卫辉 李晓龙[1,2] 何多芬[2] 曾春雨[2] 

机构地区：[1]汕头大学医学院附属第一医院心血管内科,广东汕头515041 [2]第三军医大学大坪医院心血管内科重庆市心血管病研究所

出　　处：《中华高血压杂志》2014年第11期1031-1035,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金重点项目及杰出青年基金资助项目(31130029、30925018)

摘　　要：目的探讨孕期糖尿病对子代大鼠血管内皮功能的影响及机制。方法 SD孕鼠在孕期第0天（雌鼠与雄鼠交配后见阴栓当天为孕期第0天）单次腹腔注射链菌霉素35mg/kg,对照组注射等体积生理盐水（n=6）。采用鼠尾无创血压测量法持续监测子代大鼠血压;第20周时,取肠系膜动脉,观察动脉环对乙酰胆碱（10-9~10-5 mol/L）和硝普钠（10-9~10-5 mol/L）的反应性;以一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（l-NAME,10-5 mol/L）孵育血管环30 min,观察乙酰胆碱对血管的反应以进一步探讨其作用机制;测定肠系膜动脉上内皮型一氧化氮合酶（eNOS）的蛋白表达及一氧化氮的含量。结果 12、16、20、24周龄时,链菌霉素组子代大鼠收缩压高于同龄期对照组[分别（118±4）比（105±3）,（124±2）比（114±4）,（135±3）比（118±2）,（140±4）比（120±3）mm Hg,均P〈0.01]。与对照组子代相比,链菌霉素组子代血管环对乙酰胆碱引起的最大舒张效应明显减弱[（72.2±3.3）%比（95.6±2.7）%,P〈0.05],而对硝普钠引起的最大舒张效应差异无统计学意义;l-NAME孵育后明显降低乙酰胆碱的舒血管作用;链菌霉素组子代肠系膜动脉eNOS总量不变,磷酸化表达下降;一氧化氮的含量也降低。结论孕期糖尿病致子代大鼠血压升高,其机制可能是由于血管内皮细胞一氧化氮的生成受限,进而引起血管舒张功能受损。Objective To explore the effects and related mechanisms of gestational diabetes mellitus on vascular endothelium of the offspring rats. Methods The day of vaginal plug existed firstly after the female mated with male was considered as day 0of pregnancy,when pregnant Sprague-Dawley rats received a single intraperitoneal injection of 35mg/kg streptozotocin to induce diabetes（n=6）. The control group were injected with saline（n=6）. Systolic blood pressures of the offspring were measured noninvasively and consistently. The reactivity of mesenteric arterial rings to acetylcholine（10-9-10-5 mol/L）and sodium nitroprusside（10-9-10-5 mol/L）were measured by vitro microvascular tension measurement system in 20-weeks old offspring. To estimate the effect of acetylcholine on arterial rings incubated for 30 minutes with nitric oxide synthase inhibitor（Nω-nitro-L-arginine-methyl-ester,l-NAME,10-5 mol/L）by measuring the level of endogenous endothelial nitric oxide synthase（eNOS）and nitric oxide. Results The offspring of the rats treated with streptozotocin had higher systolic blood pressure than control group at 12,16,20 and 24weeks of age[（118±4）vs（105±3）,（124±2）vs（114±4）,（135±3）vs（118±2）,（140±4）vs（120±3）mm Hg,respectively,all P〈0.01]. Compared to control group,the maximal relaxant effect of acetylcholine was significantly weakened in streptozotocin group[（72.2±3.3）% vs（95.6±2.7）%,P〈0.05],while there was no significant difference of nitroprusside caused maximal relaxant effect between the two groups.The acetylcholine induced vasodilation effect could be significantly weakened by incubating withl-NAME. In the offspring of streptozotocin group,the level of eNOS in the mesenteric arteries did not change significantly,while the phosphoeNOS expression decreased,as well as the production of nitric oxide. Conclusion Gestational diabetes mellitus induced blood pressure elevation of the offspring may related to the limited production of nitric oxide,which coul

关 键 词：孕期 糖尿病 子代 收缩压 内皮功能 

分 类 号：R714.256[医药卫生—妇产科学]