尾加压素Ⅱ对正常及缺血-再灌注离体大鼠心脏的影响

Effects of urotensin Ⅱ on isolated rat hearts under normal perfusion and ischemia-reperfusion

在正常Langendorff灌流与缺血-再灌注(停灌20 min-复灌20 min)离体大鼠心脏模型,观察尾加压素Ⅱ(urotensin Ⅱ,UⅡ)对冠脉流量、心功能和心肌代谢的影响以及心肌UⅡ受体的功能,以探讨UⅡ的心脏效应。对正常心脏给予0.1、1和10 nmol/L UⅡ各5 min,然后换洗5 min,对停灌缺血-再灌注心脏在再灌注期给予1或10nmol/L UⅡ。监测心率、左室内压和左室内压升降的最大变化率等心功能指标,计算冠脉流量,测定冠脉流出液中总蛋白和肌红蛋白含量以及乳酸脱氢酶(LDH)活性。灌流结束后,测定心肌丙二醛(MDA)含量和质膜UⅡ结合位点(放射性配基结合法)。结果如下:(1)正常心脏灌流UⅡ后,冠脉流量和心功能呈浓度依赖下降,换洗后没有完全恢复。心肌蛋白、肌红蛋白和LDH漏出随UⅡ浓度的增加而增加,换洗后迅速减少。UⅡ组心肌MDA含量与对照组差异无显著性。(2)缺血-再灌注后,冠脉流量显著减少,心功能显著抑制,再灌注期心肌蛋白、肌红蛋白和LDH明显漏出;给予UⅡ后,上述变化增强,且高浓度组更强,与对照组差异有显著性(P<<0.01),再灌注后心肌MDA含量亦显著高于对照(P<0.01)。(3)缺血-再灌注心肌质膜UⅡ受体的B_(max)显著高于正常对照心肌(14.65±1.78vs20.53±1.98 fmol/mg pr,P<0.01),Kd值变化无统计学意义。上述结果表明,在正常?

To shed light on cardiac effects of the potent vasoconstrictive peptide urotensin Ⅱ(UⅡ), Langendorff-perfused isolated rat hearts were consecutively perfused with 0.1, 1 and 10 nmol/LUⅡ, for 5 min at each dose, followed by 5-min washout. Moreover, isolated hearts subjected to 20-min global no-flow ischemia were reperfused with UⅡ(1 or 10 nmol/L) for 20 min. Heart function parameters including heart rate, left ventricular pressure and dP/dt were monitored ; content of protein and myoglobin, and activity of lactate dehydrogenase (LDH) in coronary effluent were determined; malondialdehyde (MDA) in myocardium and[^(125)I]-UⅡ binding sites in plasma membrane were measured after the completion of perfusion. The results showed that: (1) In normal rat hearts, the coronary flow was decreased and the heart function was suppressed by U Ⅱ dose-dependently, and these changes were not abolished by washout. The leakage of cardiac protein, myoglobin and LDH increased with the increment of U Ⅱ, but it diminished rapidly after washout. In contrast, MDA content in U Ⅱ-treated myocardium was not statistically different from that in normal myocardium. (2)Ischemia-reperfusion caused significant decreases in coronary flow, suppression of heart function, and leakage of protein and LDH. In UⅡ-reperfused hearts, all these disorders were significantly aggravated and myocardial MDA content significantly increased (P<0.01), to a greater extent in the presence of higher dose of UⅡ. (3) The maximal binding capacity (B_(max)) of UⅡ receptors in plasma membrane from ischemia-reperfusion myocardium increased significantly as compared with that of normal myocardium (20.53±1.98 vs 14.65±1.78 fmol/mg pr, P<0.01), while Kd remained unchanged. These results indicate that UⅡ caused injury to the isolated rat hearts under normal perfusion, and worsened the injury of the hearts under ischemia-reperfusion, in which UⅡ receptors were up-regulated.