普罗布考对缺血再灌注心肌细胞凋亡的作用

背景已发现细胞凋亡在缺血再灌注损伤中起重要作用.普罗布考除可降低血清低和高密度脂蛋白胆固醇浓度,有效治疗高胆固醇血症外,还有抗氧化活性,抑制低密度脂蛋白胆固醇的氧化修饰,减少其在血管壁沉积的作用.还有研究证明普罗布考可改善左心室功能、防止左心室扩张和减少心肌纤维化.但普罗布考保护心肌作用的确切机制尚未清楚.目的探讨普罗布考对新西兰白兔缺血再灌注心肌细胞凋亡的作用及其可能机制;并探讨其对血清超氧化物歧化酶(serum superoxide dismuase,SOD)和丙二醛水平的影响.设计随机对照的实验研究.地点、材料和干预本实验在广西医科大学医学科学实验中心完成.实验选用30只雄性新西兰白兔,白兔被随机分成3组假手术组、对照组和预治疗组,每组各10只.对照组(标准兔饲料饲养)和预治疗组(标准兔饲料饲养+普罗布考每日每只1 000 mg灌胃)各4周后建立缺血再灌注模型;假手术组(标准兔饲料饲养)4周后开胸用4-0号线穿过冠状动脉左前降支近端,但不予结扎.测定3组白兔心肌细胞凋亡指数、血清丙二醛、SOD水平.主要观察指标①普罗布考对心肌细胞凋亡的影响.②普罗布考对血清SOD和丙二醛水平的影响.结果对照组凋亡指数(34.75±3.20)%]、血清丙二醛水平(2.70±0.64)μmol/L]显著高于假手术组(0.48±0.20)%,(1.06±0.46)μmol/L,q=18.42,6.29,P＜0.01].对照组血清SOD水平显著低于假手术组(q=8.78,P＜0.01).预治疗组凋亡指数和血清丙二醛水平明显低于对照组(q=9.17,4.68,P＜0.01),血清SOD水平高于与对照组(q=3.02,P＜0.05).结论普罗布考降低缺血再灌注心肌细胞凋亡,这一保护作用可能部分是通过减少血清丙二醛水平和提高血清SOD水平来实现的.

Effects of probucol on ischemic reperfusion cardiomyocyte apoptosis

BACKGROUND: Apoptosis has been found to play an important role in ischemic reperfusion injury. Probucol can lower the serum concentrations of low-and high-density lipoprotein cholesterol(HDL-C), and treats hypercholesterolemia effectively. Probucol also has antioxidant activity, which may inhibit the oxidative modification of low-density lipoprotein cholesterol that contributes to lipid deposition in blood vessel walls. Studies have demonstrated that probucol can improve left ventricular function, prevent left ventricular dilatation and reduce cardiac fibrosis. However, the exact mechanism of probucol on cardioprotective effect is not known.OBJECTIVE: To explore the effect of probucol on ischemia reperfusion-induced cardiomyocyte apoptosis and its possible mechanism, the changes of total activity of serum superoxide dismuase(SOD) and serum level of malondialdehyde (MDA) in New Zealand White rabbits.DESIGN: Random-controlled experimental study.SETTING, PARTICIPANTS and INTERVENTIONS: The experiment was performed in the Medical Scientific Research Center, Guangxi Medical University. Thirty male New Zealand White rabbits were selected and randomized into three groups: sham group, control group and pretreated group,each involved ten rabbits. Ischemia reperfusion models were established four weeks after the animals in the control group and pretreated group were fed daily with standard rabbit diet and standard rabbits diet + probucol(1 000 mg per animal) respectively. In the sham operation group (standard rabbit diet), the chest had been opened and the left anterior descending branch of coronary artery was cut through with 4 - 0 thread without ligation. The cardiomyocyte apoptosis index, serum MDA and SOD level were assayed.MI AN OUTCOME MEASURES: The effect of probucol on cardiomyocyte apoptosis and the effect of probucol on serum SOD and MDA.RESULTS; Apoptotic index(34.75 ±3.20)% ], serum MDA(2.70 ±0.64) μmol/L] in the control group were significantly higher than those in the sham operation group, (34.75 ±3.20)%, (1.06 ±0.46)%, q = 18.42,6.29, P ＜ 0. 01 ]. Serum SOD level in the control group was significantly lower than that in the sham operation group( q = 8. 78, P ＜ 0. 01). Apoptotic index and serum MDA level in the pretreatment group were significantly lower than those in the control group ( q = 9.17, P＜0.01 ), while serum SOD level was higher compared with the control group( q = 3.02, P＜0.05).CONCLUSION: Probucol can reduce ischemia reperfusion-induced myocyte apoptosis. This protective effect may be partly due to an increase in the serum SOD activity and a decrease in serum MDA level.