不同β-受体阻滞剂抗家兔动脉粥样硬化作用的研究

EXPERIMENTAL STUDY OF THE EFFECT OF METOPROLOL AND CARVEDILOL AGAINST ARTEROSCLEROSIS

目的 探讨卡维地洛和不同剂量美托洛尔的抗动脉粥样硬化作用及其机制，并对二者的疗效作一对比。方法 雄性新西兰大耳白兔40只，随机分为正常组、高脂组、小剂量美托洛尔组、大剂量美托洛尔组、卡维地洛组，每组8只，分别按不同方法喂养10周。实验结束后，分别检测各组家兔血清超氧化物歧化酶（SOD）的活性及丙二醛（MDA）的含量。采用免疫组化的方法分别测定各组血管壁增殖细胞核抗原（PCNA）及核因子kBp65（NFkBp65）的表达。结果 与正常组比较，高脂组血清SOD活性降低，MDA含量增加，差异有显著性（F=8．40、41．22，q=3．81、11．27，P〈0．05）；高脂组，小、大剂量美托洛尔组血清SOD活性和MDA含量比较差异无统计学意义（q=0．28～0．41，P〉0．05）；与高脂组及小、大剂量美托洛尔组比较，卡维地洛组血清SOD活性明显升高，血清MDA含量明显下降（q=1．13～9．45，P〈0．05）。高脂组血管壁PCNA和NFkBp65的表达较正常组明显增加（F=138．46、78．67，q=54．32、32．59，P〈0．05）；高脂组及小、大剂量美托洛尔组、卡维地洛组血管壁PCNA和NFkBp65的表达依次减少，差异有显著性（q=28．89～78．41，P〈0．05）。相关分析表明，各组PCNA和NFkBp65水平呈正相关（r=0．975，P〈0．01）。结论 美托洛尔与卡维地洛均具有抗动脉粥样硬化的作用，美托洛尔抗动脉粥样硬化的作用呈剂量依赖性；卡维地洛抗动脉粥样硬化的效应优于美托洛尔，其原因可能是卡维地洛具有较强的抗氧化作用。

Objective To investigate the mechanism of carvedilol and metoprolol in different doses against arterosclerosis and compare their therapeutic effect. Methods Male New Zealand white rabbits （n=40） were randomly and evenly divided into five groups： normal group, high-fat-diet group, low-dose-metoprolol group, high-dose-metoprolol group and cavedilol group. Ten weeks later, levels of serum superoxide dismutase （SOD） and malondiadehede （MDA） were measured. Expression of PCNA and NFkBp65 in aorta was detected by immunohistochemistry. Results Compared with the normal group, lower level of serum SOD and higher level of serum MDA were found in the high-fat-diet group （F=8.40,41.22;q=3.81,11.27;P〈0.05）. No statistical differences were observed among the levels of serum SOD and MDA between the high-fat-diet group and metoprolol group either in low or high dose （q=0. 28-0.41, P〉0.05）, but higher levels of serum SOD and lower levels of serum MDA were found in carvedilol group, compared with the other four groups （q=1. 13-9.45, P〈0.05）. Expression of PCNA and NFkBp65 in the aorta of the high-fat-diet animals was obviously stronger than those of the normal group （F= 138. 46,78.67 ;q= 54.32,32.59; P〈0.05）. There existed a decreasing gradient in the expression of PCNA and NFkBp65 among the animals of high fat diet, low-dose metoprolol, high-dose metoprolol and cavedilol group （q=28.89-78.41, P〈0.05）. A positive correlation was found in the expression of PCNA and NFkBp65 among the five groups （r=0. 975, P〈0.01）. Conclusion Both metoprolol and cavedilol posses anti-arteroscleotic effect and metoprolol is of dose-dependent. Carvedilol is better than metoprolol due to its stronger anti-oxidative effect.