钙敏感受体(CaR)调节动脉粥样硬化斑块形成的机制研究  

Mechanism of atherosclerotic plaque formation affected by calcium-sensing receptor

作　　者：王毅[1] 李莹[2] 李晨光[2] 张凤香[2] 

机构地区：[1]辽宁医学院附属第三医院检验科,辽宁锦州121001 [2]辽宁医学院附属第一医院心外科,辽宁锦州121001

出　　处：《现代预防医学》2014年第21期3979-3982,共4页Modern Preventive Medicine

基　　金：辽宁省自然科学基金(2013022010);辽宁医学院青年科技启动基金项目(Y2012Z011);辽宁医学院附属第一医院青年科技启动基金项目(FY2012-07)

摘　　要：目的观察钙敏感受体（CaR）的表达变化对动脉粥样硬化斑块形成的影响。方法 30只ApoE-/-小鼠,体重18~25 g,随机选择10只分为空白对照组、CaR激动剂（GdCl3）（50 mg/kg）组、CaR抑制剂（NPS2390）（100 mg/kg）组以灌胃的方式给药,每周2次,高脂饮食10周后处死;通过腹主动脉介入方法测量血压;通过全自动生化分析仪及血生化测定试剂盒检测总TC、TG、HDL含量和LDL含量;光镜下观测各组大鼠颈动脉横切面测量颈动脉内膜和中膜厚度。ELISA法检测血清血管细胞粘附分子-1（VCAM-1）、单核细胞趋化蛋白-1（MCP-l）和外周血管假性血友病因子（vWF）水平;Western blot检测细胞内细胞间粘附分子-1（ICAM-1）和CC类趋化因子受体2（CCR2）蛋白的表达情况。结果与空白对照组比较,GdCl3组内膜增厚程度、中膜脂质的沉积范围和TC、TG和LDL水平均明显降低,而HDL明显升高;NPS2390组内膜增厚程度、中膜脂质的沉积范围和血压、TC、TG和LDL均明显升高,而HDL水平明显降低;ELISA法检测结果显示：与空白对照组比较,GdCl3组上清中VCAM-1、MCP-1和vWF含量均明显降低;而NPS2390组细胞培养的上清中VCAM-1、MCP-1和vWF含量均明显增加;Western blot检测结果发现：与空白对照组比较,GdCl3组ICAM-1和CCR2的表达均明显下降;而NPS2390组ICAM-1和CCR2的表达均明显增强（P〈0.05）。结论 CaR可以通过影响相关炎性因子的分泌和蛋白的表达来抑制动脉粥样硬化斑块的形成。Objective To observe the effect of calcium-sensing receptor （CAR） expression on the formation of atherosclerotic plaque expression. Methods 30 ApoE-/ - mice, weighing 18-25g, were randomly divided to the control group （n=10）, the GdC13 （50mg/kg） group （n--10）, and the NPS2390 （100mg/kg） group （n=10）. The mice were administered orally every twice a week and fed with high-fat food for 10 week and then sacrificed; Blood pressure was measured by intervention of abdominal aorta; TC, TG, HDL levels and LDL levels were measured by automatic biochemical analyzer and blood biochemistry assay kit; The thickness of internal tunica and media tunica of carotid artery were observed by microscope of each group. VCAM-1, MCP-I and vWF levels were measured by ELISA; intra and inter cellular expression of ICAM-1 and CCR2 protein were measured by Western blot. Results Compared with the control group, the increased thickness of internal tunica, lipid area of media tunica, TC, TG and LDL levels were significantly decreased, while HDL level increased significantly in the GdC13 group; the increased thickness of internal tunica, hpid area of media tunica, TC, TG and LDL levels, and the blood pressure were significantly increased, while HDL level decreased significantly in the NPS2390 group; The ELISA results showed that compared with the control group, VCAM-1, MCP-1 and vWF levels were significantly reduced in the GdC13 group supernatant, but significantly increased in the NPS2390 group. Western blot results showed that compared with the control group, ICAM-1 and CCR2 expression were significantly decreased in the GdC13 group but significantly increased in the NPS2390 group （P〈0.05）. Conclusion CaR can inhibit the formation of atherosclerotic plaques by the expression of inflammatory cytokines and related proteins.

关 键 词：钙敏感受体 血管细胞粘附分子-1 单核细胞趋化蛋白-1 外周血管假性血友病因子 

分 类 号：R113[医药卫生—公共卫生与预防医学]