儿茶素靶向磷酸二酯酶缓解大鼠心力衰竭机制的研究

A Study on Catechin Targeted on Phosphodiesterase in Alleviation of Heart Failure in Rats

目的探讨磷酸二酯酶(PEDs)抑制剂儿茶素缓解大鼠心力衰竭的机制。方法采用酶抑制动力学方法,研究儿茶素对PEDs的抑制作用和抑制动力学。SD大鼠随机分为对照组、模型组和不同剂量(0.05、0.2、0.4 mmol/L)儿茶素治疗组,模型组应用阿霉素制备心力衰竭动物模型,不同剂量儿茶素治疗组在造模前给予儿茶素处理。观察5组心肌细胞凋亡率、血流动力学和血清心钠肽(ANP)、脑钠肽(BNP)水平。结果儿茶素对PDEs的半数抑制浓度(IC50)为(0.063±0.01)mmol/L,随着儿茶素浓度的增加,其对PDEs的延滞时间逐步升高;其抑制作用类型为典型的竞争性抑制。模型组心肌细胞凋亡率高于对照组,不同剂量儿茶素组低于模型组(P<0.05),模型组中心静脉压(CVP)和右心室收缩压(RVSP)高于对照组,右心室压力最大上升速度(RV dp/dt_(max)),平均主动脉压(MAP)和左心室压力上升最大变化速度(LV dp/dt_(max))均低于对照组,0.2、0.4 mmol/L儿茶素组CVP、RVSP低于模型组,RV dp/dt_(max)、MAP、LV dp/dt_(max)均高于模型组(P<0.05);模型组ANP、BNP含量高于对照组,儿茶素不同剂量组均低于模型组(P<0.05)。结论儿茶素能够通过竞争PEDs的活性位点,使PEDs的催化活性降低而产生催化延迟效应,最终起到缓解心力衰竭的作用。

Objective To investigate inhibitory mechanisms of Catechin targeted on Phosphodiesterases （ PEDs） in alleviation of heart failure in rats. Methods Inhibition effect and dynamics of Catechin on PEDs were studied using enzyme inhibition dynamics method. SD rats were randomly divided into control group, model group and different dosage Catechin groups （0. 05, 0. 2 and 0. 4 mmol/L）. Model group was given Adriamycin for preparation animal models of heart failure, and different dosage Catechin groups were given Catechin treatment before and after model establishment. Levels of cardiac myocyte apoptosis rate （ CMAR） , haemodynamics, atrial natriuretic peptide （ ANP） and brain natri-uretic peptide （BNP） were observed in five groups. Results Inhibitory concentration 50 （IC50） of Catechin on PDEs was （0. 063 ± 0. 01）mmol/L, and delay time of Catechin on PDEs was gradually escalated with increasing Catechin con-centration, and inhibition type was typically competitive inhibition. CMAR level in model group was higher than that in control group, while the levels in different dosage Catechin groups were lower than that in model group （P＆lt;0. 05）. In model group, levels of central venous pressure （ CVP） and right ventricular systolic pressure （ RVSP） were higher, while levels of RV dp/dtmax , MAP and LV dp/dtmax were lower than those in control group, levels of central venous pressure （CVP） and right ventricular systolic pressure （RVSP） in 0. 2 and 0. 4 mmol/L Catechin groups were lower, while levels of right ventricle maximum rate of pressure rise （ RV dp/dtmax ） , mean arterial blood pressure （ MAP） and left ventricle maximum rate of pressure rise （LV dp/dtmax） were higher than those in model group （P＆lt;0. 05）;ANF and BNP contents in model group were lighter than those in control group, but the contents in different dosage Catechin groups were less than those in model group （P＆lt;0. 05）. Conclusion Catechin can have catalytic delaying effect by decreasing PEDs cat-alytic activity after Catechin competing on PEDs active site, so that alleviation of heart failure can be achieved.