巯基修饰剂对硫化氢的离体心脏灌流效应的影响

The significance of hydrosulfide modifier in the regulation of cardiac function by hydrogen sulfide

目的观察巯基氧化剂及还原剂对大鼠离体心脏心功能的影响,以探讨巯基氧化剂二酰胺(diamide)及还原剂二硫苏糖醇(DL-dithiothreitol,DTT)对心肌活动的调节意义,并观察其对硫化氢的离体心脏灌流效应的影响。方法应用Langendorff灌流大鼠离体心脏,用生理浓度NaHS(100μmol.L-1)持续灌流20 min,测量心率(HR)、左室内压差(△LVP=左室收缩压-左室舒张压)、左室内压变化速率(±dp/dtmax)、冠脉灌流量(CPF)等指标;分别应用Diamide及DTT预灌流,后给予生理剂量NaHS灌流,观察其是否可以阻断NaHS的效应。结果生理剂量NaHS持续灌流20min内,可以明显抑制±dp/dtmax及△LVP(P<0.05),而对HR、CPF几乎没有影响。巯基氧化剂二酰胺可以大部分阻断H2S的心脏功能负性调节效应,而经巯基还原剂DTT灌流后,H2S可以发挥负性调节作用。结论内源性H2S可能通过作用于心肌组织蛋白质中Cys-SH位点,产生心肌的负性调节作用。

Aim To observe the role of hydrosulfide oxidizer Diamide and reducer DTT in the regulation of cardiac function isolated perfused heart of rat with H2S. Methods Langendorff apparatus was used to perfuse the rat heart in vitro. After 20 minutes of stabilization, physiological concentration of HaS （100 μmol · L^-1） was continuously perfused for 20 min. Heart rate （HR）, difference of left ventricular pressure （△LVP）, left ventricular peak rate of contraction （＋dp/dt ） and peak rate of relaxation （ -dp/ dtmax ） and coronary perfusive flow （CPF） were measured. Hydrosulfide oxidizer diamide and reducer DTT were perfused in advance respectively, then Naris at physiological concentration was used. The effectiveness of hydrosulfide oxidizer diamide and reducer DTT on cardiac function regulated by H2S were analyzed. Results Continuous perfusion of NariS at physiological concentration for 20 min inhibited left ventricular ＋ dp/dtmax, △ LVP significantly, but HR and CPF did not alter. Negative inotropic effect of H2S could partly be blocked by hydrosulfide oxidizer diamide; however, negative inotropic effect of H2S could not be blocked by hydrosulfide reducer DTT. Conclusion Endogenous H2S can produce negative inotropic effect, and act as a physiological cardiac function regulator, which is mediated by Cys-SH situs of rat myocardium.