生长激素释放激素受体激动剂MR409减轻糖尿病Db/Db小鼠血管钙化  

Growth hormone releasing hormone receptor agonist MR409 attenuates vascular cal-cification in diabetic Db/Db mice

作　　者：薛锐泽 蔡瑞平 唐琪 刘月阳 徐茜 周明生 XUE Ruize;CAI Ruiping;TANG Qi;LIU Yueyang;XU Qian;ZHOU Mingsheng(Department of Physiology,Shenyang Medical University,Shenyang,Liaoning 110034,China)

机构地区：[1]沈阳医学院基础医学院生理学教研室,辽宁省沈阳市110034

出　　处：《中国动脉硬化杂志》2021年第8期661-667,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81970357);沈阳医学院博士科研启动基金项目(2018056);沈阳医学院硕士研究生科技创新基金项目(Y20190504)。

摘　　要：目的研究生长激素释放激素受体激动剂MR409对基因缺陷小鼠Db/Db糖尿病小鼠(Db/Db小鼠)血管钙化(VC)的保护作用。方法以12周龄雄性野生型(WT)C57BL/6小鼠为WT组(对照组),12周龄雄性Db/Db小鼠随机分为Db/Db组(糖尿病组)和MR409组(MR409治疗组)。MR409组隔天给予MR409(15μg/次)治疗8周。第8周末,检测小鼠血清碱性磷酸酶(ALP)和血糖水平。HE染色观察小鼠主动脉形态变化。von Kossa染色、茜素红染色检测主动脉钙盐沉积。离体血管灌流系统测定内皮依赖性血管舒张功能。免疫组织化学染色检测主动脉钙化相关蛋白Runt相关转录因子2(Runx2)蛋白表达。二氢乙锭荧光染色检测主动脉活性氧(ROS)水平。结果与WT组比较,Db/Db组血清ALP活性升高,血管壁厚度增加,血管舒张功能降低,主动脉ROS水平增加(P<0.05);与Db/Db组比较,MR409组ALP活性降低,主动脉肥厚减轻,血管舒张功能改善,主动脉ROS水平降低(P<0.05)。与WT组比较,Db/Db组有明显的VC,表现为主动脉钙盐沉积增加,Runx2蛋白表达升高(P<0.05);与Db/Db组比较,MR409组主动脉钙盐沉积减轻,Runx2蛋白表达降低(P<0.05)。结论MR409能显著抑制糖尿病小鼠VC,减轻主动脉增厚,改善血管内皮功能,其机制可能与抑制氧化应激诱导的Runx2表达升高有关。Aim To study the protective effect of growth hormone releasing hormone receptor agonist MR409 on vascular calcification(VC)in gene deficient mice Db/Db diabetic mice(Db/Db mice).Methods With 12-week-old male wild-type(WT)C57BL/6 mice as the WT group(control group),12-week-old male Db/Db mice were randomly divided into Db/Db group(diabetes group)and MR409 group(MR409 treatment group).MR409 group was given MR409(15μg/time)every other day for 8 weeks.At the end of the 8th week,the mouse serum alkaline phosphatase(ALP)and blood glucose levels were tested.HE staining was used to observe the morphological changes of aorta in mice.Calcium salt deposition in aorta was detected by von Kossa staining and alizarin red staining.Endothelium-dependent vasodilation function was measured by in vitro vascular perfusion system.Aortic calcification-related protein Runt-related transcription factor 2(Runx2)protein expression was detected by immunohistochemical staining.Aortic reactive oxygen species(ROS)level was detected by dihydroethidium fluorescent staining.Results Compared with WT group,serum ALP activity increased,blood vessel wall thickness increased,vasodilation function decreased,and aortic ROS level increased in Db/Db group(P<0.05).Compared with Db/Db group,ALP activity decreased,aortic hypertrophy decreased,vasodilation function improved,and ROS level of aorta decreased in MR409 group(P<0.05).Compared with WT group,there was significant VC in Db/Db group,which showed increased calcium salt deposition and increased Runx2 protein expression in aorta(P<0.05).Compared with Db/Db group,calcium salt deposition and Runx2 protein expression in aorta were decreased in MR409 group(P<0.05).Conclusion MR409 can significantly inhibit VC,reduce aortic hypertrophy and improve vascular endothelial function in diabetic mice,and its mechanism may be related to the inhibition of the increase of Runx2 expression induced by oxidative stress.

关 键 词：生长激素释放激素受体激动剂 MR409 血管钙化 钙盐沉积 Runt相关转录因子2 血管舒张 DB/DB小鼠 

分 类 号：R363[医药卫生—病理学] R54[医药卫生—基础医学]