兔动脉粥样硬化组织COX-2、mPGES-1表达及阿伐他汀的影响

目的通过观察环氧化酶Ⅱ(cyclooxygenase-2,COX-2)、诱导型前列腺素合成酶Ⅰ(membrane associatedprostaglandin E-1,mPGES-1)在兔动脉粥样硬化(AS)斑块中的表达水平及阿伐他汀对其的干预作用。方法取40只体质量为2.0～2.2 kg的3月龄健康雄性新西兰兔,随机分为正常对照组8只(普通饲料);高脂模型组32只(高胆固醇饲料)。8周后将高脂模型组再分为模型组、阿伐他汀治疗Ⅰ组、Ⅱ组及Ⅲ组[剂量分别为2.5、5及10 mg/(kg.d),n=8]。6周后取各组兔冠状动脉,检测其COX-2及mPGES-1的表达;同时,采血检测各组血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及极低密度脂蛋白胆固醇(VLDL-C)浓度。结果模型组血清TC、TG、HDL-C、LDL-C及VLDL-C水平与正常对照组比较差异显著(P<0.05);而阿伐他汀治疗Ⅱ组及Ⅲ组上述各项指标与模型组比较差异显著(P<0.05);阿伐他汀治疗Ⅰ组各项血脂水平较之模型组无显著差异(P>0.05)。与正常对照组比较,模型组动脉粥样硬化组织的COX-2及mPGES-1表达显著增高(P<0.05);与模型组比较,治疗Ⅱ组、Ⅲ组动脉粥样硬化组织的COX-2及mPGES-1表达明显下调(P<0.05)。结论阿伐他汀可能通过降低COX-2/mPGES-1表达、降低血脂,进而发挥其对AS的治疗作用。

Expression of COX-2 and mPGES-1 in rabbit coronary atherosclerotic tissues and effects of atorvastatin

Objective To determine the expression of cyclooxygenase-2(COX-2) and membrane associated prostaglandin E-1(mPGES-1) in a rabbit model of atherosclerosis and determine the effects of ator-vastatin on the expression.Methods Forty male New Zealand rabbits(3 months old) were fed with normal diet(blank-control group,n=8) and high-cholesterol diet(n=32) respectively for 8 weeks.Then,the high-cholesterol diet rabbits were subsequently assigned to receive non-treatment(simple atherosclerotic model group),and treatment groups with atorvastatin at 2.5,5 and 10 mg/(kg·d) respectively(n=8 for each group).Six weeks later,all rabbits were sacrificed and their coronaries were removed.The expression of COX-2 and mPGES-1,and serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C) and very low-density lipoprotein cholesterol(VLDL-C)were evaluated respectively.Results Compared with the blank-control group,the expression levels of COX-2 and mPGES-1,and the serum levels of total TC,TG,LDL-C and VLDL-C were all significantly increased,and HDL-C was significantly reduced in model group(P<0.05).After being treated by atorvastatin with 5 mg/(kg·d) and 10 mg/(kg·d),the levels of COX-2 and mPGES-1,and TC,TG,LDL and VLDL were significantly decreased,but HDL was increased compared with the corresponding values of the model rabbits(P<0.05).Conclusion Atorvastatin may play anti-atherosclerotic inflammation role through down-regulating COX-2/mPGES-1 and reducing blood lipid.