不同β受体阻滞剂对大鼠心肌间隙连接结构作用的对比研究

The effects of various β-blockers on myocardial gap junction structure in rat with myocardial ischemia-reperfusion injury

目的比较三代β受体阻滞剂的代表药物卡维地洛、美托洛尔及普萘洛尔对大鼠心肌缺血再灌注损伤心肌间隙连接(GJ)结构的不同作用。方法将大鼠随机分为假手术组、缺血再灌注组、卡维地洛组、美托洛尔组及普萘洛尔组。除假手术组只穿线不结扎外,其余各组均结扎左冠状动脉前降支30 min,然后松开结扎线复灌4 h,建立心肌缺血再灌注损伤模型。于再灌4 h 末用免疫荧光和激光扫描共聚焦显微镜技术观察心肌间隙连接蛋白43(CX43)的分布及组成变化,用激光扫描共聚焦显微镜对 CX43进行定量。结果与假手术组相比,缺血再灌注组 CX43-GJ 结构明显异常。与缺血再灌注组比较,卡维地洛组、美托洛尔组和普萘洛尔组 CX43-GJ 损伤减轻。各药物治疗组间比较,卡维地洛组 CX43-GJ 结构损伤最轻。结论各种β受体阻滞剂均具有保护心肌 GJ 结构的作用,以卡维地洛的作用最明显。

Objective To compare the effects of carvedilol, metoprolol and propranolol on myocardial gap junction （GJ） structure in rat with myocardial ischemia and reperfusion injury. Methods Rats were divided randomly into five groups： sham operation group （SO）, myocardial ischemia and reperfusion group （IR）, IR ＋ carvedilol group （ CV）, IR ＋ metoprolol group （ MT）, and IR ＋ propranolol group （PP）. The left anterior descending branch was ligated for 30 minutes and reperfused for 4 hours （IR）. After 4 h reperfusion, the distribution and composition of gap junctional connexin 43 （CX43） were observed by immunofluorescence and laser scanning confocal microscopy （LSCM）, and the quantification of CX43 was measured by LSCM. Result Compared with SO group, IR resulted in abnormal distribution and composition of CX43-GJ and the impairment of CX43-GJ was significantly attenuated by CV, MT and PP treatments with the best effect observed in CV group （ P 〈 0.05 vs. MT and PP）. Conclusion These results suggest that β-blokers, especially, carvedilol, could significantly attenuate IR induced CX43-GJ impairment.