目的:观察Rho激酶对失血性休克大鼠心肌收缩力的影响.方法:利用离体乳头肌张力测定技术和心脏灌流技术,测定失血性休克后不同时间大鼠离体左室乳头肌在K-H液中的等长收缩张力的变化,以及大鼠的血流动力学指标(包括LVSP、±dp/dtmax),并观察Rho激酶在其中的作用.结果:失血性休克后大鼠离体乳头肌收缩力和离体心脏血流动力学指标随着休克时间延长逐渐降低,在休克1 h、2 h以及4 h时乳头肌对异丙肾上腺素的收缩反应性显著低于正常对照组,同时休克后不同时点心肌组织Rho激酶活性发生明显变化,在休克1 h、2 h、4 h Rho激酶活性显著低于正常对照组,Rho激酶活性变化与大鼠离体乳头肌收缩力和离体心脏血流动力学参数变化之间呈明显相关性,Rho激酶激动剂U-46619在浓度为10-8 mol/L预孵育休克2 h离体乳头肌或离体心脏后,离体乳头肌对异丙肾上腺素收缩力明显增加,最大收缩张力显著高于休克2 h组,曲线向左移.U-46619也可明显改善休克离体心脏血流动力学指标,Rho激酶特异性抑制剂Y-27632可明显拮抗由U-46619引起的休克大鼠离体乳头肌收缩反应性和离体心脏的改善作用.结论:Rho激酶在休克心肌收缩功能调节中发挥重要作用.
AIM: To explore the role of Rho kinase in myocardium contraction in hemorrhagic shock rats. METHODS: The rat cardiac papillary muscle and rat heart at different time points during hemorrhagic shock were isolated. The contraction of papillary muscle in response to isoprenaline and the hemodynamic parameters of the isolated hearts in vitro including left intraventricular systolic pressure (LVSP), the maximal change rate of left intraventricular pressure ( + dp/dtmax ) were measured. RESULTS : The activity of Rho kinase, the contractile response of cardiac papillary muscle to isoprenaline and the hemodynamic parameters of the hearts were decreased gradually at the 1 h, 2 h and 4 h after shock. Compared to the normal controls, the activity of Rho kinase, the contractile response of cardiac papillary muscle and the hemodynamic parameters of the hearts were decreased significantly. The change of Rho kinase was positively correlated with the contractile response and the hemodynamic parameters of the heart. Stimulation with U -46619 at concentration of 10-s mmol/L increased the activity of Rho kinase and improved the contractile response of cardiac papillary muscle to isoprenaline and the hemodynamic parameters of the isolated heart. The effects of U -46619 on the above parameters were abolished by Rho kinase specific inhibitor Y -27632 at concentration of 10-5 mol/L. CONCLUSION: Rho kinase plays an important role in the regulation of cardiac contractility during hemorrhagic shock.