缝隙连接在维持血管张力及损伤血管修复中的作用  

Role of gap junctions on the regulation of vascular tension and the repair of vascular injury

作　　者：王捷琼 谭霞 于学军 陈剑飞 宋明宝 WANG Jieqiong;TAN Xia;YU Xuejun;CHEN Jianfei;SONG Mingbao(Institute of Cardiovascular Disease of People＇s Liberation Army,Xinqiao Hospital,Army Medical University,Chongqing 400037,China)

机构地区：[1]中国人民解放军陆军军医大学新桥医院全军心血管病研究所

出　　处：《中国动脉硬化杂志》2018年第9期877-882,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(30570765)

摘　　要：目的探讨缝隙连接在维持血管张力及损伤血管修复中的作用。方法取大鼠主动脉制成血管环分别测量在18α-甘草次酸（18α-GA）作用前后血管环对去甲肾上腺素（NE）和乙酰胆碱（Ach）反应性变化;建立大鼠颈动脉损伤模型,给予生胃酮3 mg/（kg·d）腹腔注射,对照组给予生理盐水腹腔注射（2 m L/d）,14天后处死动物,用HE和DAPI-伊文思蓝染色观察新生内膜厚度,细胞免疫荧光染色法及Western blot检测靶血管缝隙连接蛋白43（Cx43）的表达。结果单纯给予18α-GA处理血管环并未出现明显的收缩或舒张反应。对照组给予去甲肾上腺素或乙酰胆碱后血管环发生明显的收缩或舒张反应,而经18α-GA预处理后,去甲肾上腺素或乙酰胆碱引起的血管环收缩或舒张反应显著降低（去甲肾上腺素：0.60±0.03比0.21±0.04;乙酰胆碱：0.15±0.01比0.62±0.03; P〈0.05）。损伤2周生胃酮干预组血管新生内膜增生明显减少,血管腔狭窄减轻。生胃酮干预组新生内膜细胞核数量显著低于对照组（89±28比236±15,n=5,P〈0.01）。免疫荧光染色显示,在形成的新生内膜中Cx43表达丰富。Western blot结果显示,生胃酮干预组Cx43的表达显著低于对照组（0.38±0.11比0.93±0.06,n=3,P〈0.01）。结论缝隙连接在生理条件下参与维持及调节血管张力,在病理条件下能够促进血管损伤后新生内膜的过度增生,在血管损伤性疾病的发生、发展过程中具有重要作用。Aim To explore the role of gap junctions on the regulation of vascular tension and the repair of vascular injury. Methods Vascular rings from rat carotid artery were made and used to compare to the changes of vascular response to norepinephrine（NE） or acetylcholine（Ach） with or without 18α-GA. The model of vascular injury was established with rat carotid balloon injury. And animals were administrated with intraperitoneal injections of carbenoxolone（3 mg/（kg·d）） in carbenoxolone group or saline（2 m L/d） in control group for 2 weeks after carotid balloon injury.After 2 weeks,HE staining and DAPI-Evens blue double staining were applied to evaluate the neointimal formation of targeted vessels. And cell immunofluorescence staining and Western blot were used to detect connexin 43（Cx43） expression on targeted vessels. Results 18α-GA alone didn＇t cause significant response of vascular rings to systole or diastole.In control group,NE or Ach could induce vascular rings to contract or relax,but 18α-GA could inhibit the contraction or relaxation of vascular rings triggered by NE or Ach（NE： 0.60±0.03 vs. 0.21±0.04; Ach： 0.15±0.01 vs. 0.62±0.03; P〈0.05）. 2 weeks after carotid balloon injury,carbenoxolone could significantly reduce the neointimal formation and the stenosis of blood vessel lumen. The number of neointimal nuclei in the carbenoxolone group was significantly lower than that in the control group（89±28 vs. 236±15,n = 5,P〈0.01）. Immunofluorescence staining showed that Cx43 was abundant in neointima. Western blot results also suggested that the expression of Cx43 in the carbenoxolone group was significantly lower than that in the control group（0.93±0.06 vs. 0.38±0.11,n = 3,P〈0.01）. Conclusions Gap junctions participate in maintaining and regulating vascular tension under the physiological condition,and promote the neointimal formation after vascular injury under the pathological condition. Hence,gap junctions play a key role on the development and progression

关 键 词：缝隙连接 血管张力 损伤血管修复 内膜增生 

分 类 号：R363[医药卫生—病理学]