尾加压素Ⅱ对大鼠心功能的影响及电生理机制探讨

The Effect of Urotensin Ⅱ on Cardiac Function of Rats and Its Electrophysidogical Mechanism

目的探讨尾加压素Ⅱ(UⅡ)对大鼠心功能的影响及可能的电生理机制。方法在Langendorff离体心脏灌注的模型上,观察给予不同浓度的UⅡ后大鼠心功能的变化;利用全细胞膜片钳技术,观察给予不同浓度的UⅡ灌流5min后,大鼠心肌细胞L-型钙电流(ICa-L)密度的变化。结果给予不同浓度的UⅡ(10-9 mol/L～10-6 mol/L)灌注大鼠心脏后,左心室压最大上升速率(+dp/dtmax)分别降低25.60%、31.48%、34.36%、37.47%,左心室压最大下降速率(-dp/dtmax)分别降低33.61%、46.10%、51.76%、58.32%。运用全细胞膜片钳技术,在单个心肌细胞上给予不同浓度的UⅡ(10-9 mol/L～10-5 mol/L)灌流5min后,ICa-L峰值分别下降为(6.70±1.78)pA/pF、(5.93±2.02)pA/pF、(5.40±2.15)pA/pF、(4.54±2.00)pA/pF、(3.80±1.82)pA/pF,与对照组(8.03±1.20)pA/pF相比,差异有统计学意义(P<0.05或P<0.01)。结论 UⅡ呈浓度依赖性的抑制大鼠心功能并减弱心肌细胞L-型钙电流强度;UⅡ可能通过抑制心肌细胞L-型钙电流而发挥其心功能抑制作用。

Objective To investigate the effects of urotensin Ⅱ（UⅡ） on cardiac function and L-type calcium current in rats,and then to study the probably electrophysiological mechanism of UⅡ＇s effect on the heart of rats.Methods Hearts were perfused in the Langendorff mode,and changes of cardiac function were observed after UⅡ was perfused in different concentrations.Whole-cell patch clamp technique was used to investigate the changes of L-type calcium current（ICa-L） of cardiomyocytes in rats five minutes after perfusion by different concentrations of UⅡ.Results After perfusion by UⅡ（10-9 mol/L～10-6 mol/L）,＋dp/dtmax was decreased by 16.48%,25.53%,31.53%,and 34.47%,respectively.The-dp/dtmax was decreased by 22.78%,33.63%,46.09% and 51.73%,respectively.At five minutes after perfusion at different concentrations of UⅡ（10-9 mol/L～10-5 mol/L）,peak values of ICa-L was expressed a decrease trend in single cardiomyocytes investigated by whole-cell patch clamp technique.These values were decreased to（6.70±1.78） pA/pF,（5.93±2.02） pA/pF,（5.04±2.15） pA/pF,（4.54±2.00） pA/pF,and（3.80±1.82） pA/pF compared with（8.03±1.20） pA/pF in control group（P〈0.05 or P〈0.01）.Conclusion UⅡ exerts a dose-dependent inhibitory effect on cardiac function and has negative effect on L-type calcium current of cardiomyocytes.UⅡ probably inhibits cardiac function by inhibit L-type calcium current on cardiomyocytes.