丙丁酚对动脉粥样硬化小鼠抗氧化作用的比较  

Comparison of Antioxidant Effects of Probucol in Atherogenic Mice

作　　者：叶延平[1] 莫中成[2] 龙治峰[2] 尹小波[3] 李霞[3] 张青海[3] 李媛彬[3] 易光辉[3] 

机构地区：[1]南华大学公共卫生学院 [2]南华大学组织胚胎学教研室 [3]南华大学心血管疾病研究所暨动脉硬化学湖南省重点实验室,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2008年第7期513-518,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30570958);湖南省卫生厅课题(B2005-093)

摘　　要：目的观察丙丁酚对高脂高胆固醇饲养的C57BL/6J小鼠和载脂蛋白E基因缺陷(载脂蛋白E-/-)小鼠抗氧化作用的影响,比较丙丁酚对两种小鼠的作用差异。方法以高脂高胆固醇饲料饲喂小鼠,制作高脂血症模型。采用酶比色法及相关检测试剂盒分别测定小鼠血脂水平及与氧化应激相关的指标;采用双抗夹心ELISA法测定氧化型低密度脂蛋白的水平;采用改良的Eckerson方法测定对氧磷酶1的活性,采用逆转录聚合酶链式反应检测对氧磷酶1mRNA的表达。结果与两种小鼠各自的基础饲料组比较,高脂高胆固醇组血脂水平均有升高;与各自的高脂高胆固醇组比较,丙丁酚处理后,C57BL/6J小鼠血清的甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平分别降低了41.0%、43.6%、44.8%和41.3%(P<0.05),载脂蛋白E-/-小鼠血清的甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平,分别降低了36.2%、28.2%、31.3%、33.9%(P<0.05)。小鼠主动脉内膜的动脉粥样硬化病变与各自高脂高胆固醇组比较,C57BL/6J小鼠经丙丁酚处理后病变面积减少了61.1%,载脂蛋白E-/-小鼠经丙丁酚处理后病变面积减少了27.2%(P<0.05)。与各自基础饲料组比较,高脂血症小鼠丙二醛及氧化型低密度脂蛋白的水平增高,而总抗氧化能力和超氧化物歧化酶水平降低(P<0.05);与各自的高脂高胆固醇组比较,丙丁酚处理组小鼠的总抗氧化能力和超氧化物歧化酶水平上升,丙二醛及氧化型低密度脂蛋白的水平则降低(P<0.05)。两组小鼠高脂高胆固醇组血清对氧磷酶1的活性较基础饲料组均下降,经高脂饮食加丙丁酚处理后对氧磷酶1活性比单纯高脂饮食组有所增加;肝脏对氧磷酶1mRNA的表达在高脂高胆固醇组下调,而丙丁酚处理组则上调(P<0.05)。结论丙丁酚可以减轻高脂血症小鼠动脉粥样硬化病变,减轻高脂高胆固醇饮食诱Aim To investigate the effects of probucol on high fat-high cholesterol （HFHC） diet-induced hyperlipidemia and oxidative stress in apo E deficient（ apoE^-/- ） mice and genetic background C57BL/6J mice. Methods The hyperlipidemic mice were induced by feeding HFHC diet which was supplemented with 15%lard and 0.25% cholesterol. The levels of plasma lipids were determined by standard assays. The oxidative stress was evaluated by the serum levels of total antioxidant capacity （T-AOC）, superoxide dismutasc （SOD）, and malonic dialdehyde （MI）A） determined by commercially provided kits. The aortic atheresclerotic lesions were demonstrated by Sudan Ⅳ staining. Activity of paraoxonase 1 （PON1） was assessed by modified Echerson＇s method. Expression level of PON1 in liver was evaluated by semi-quantitative reverse-transcription-polymerase reaction （RT-PCR）. Results HFHC diet elevated the levels of serum triglycefide （TG）, total cholesterol （TC）, low density lipoprotein-cholesterol（LDLC）, and high density lipoprotein-cholesterol （HDLC）. Probucol decreased the elevation of serum levels oflipids. In C57BL/6J mice, the levels OfTG, TC, LDLC, and HDL-C lowered41%, 43%, 44.8%, and41.3%, respectively, compared with controlgroup （P〈0.05）. InapoE^-/- mice, decrease of 36.2%, 28.2%, 31.3%, and33. 9%, respectively, was observed versus apo E^-/- control （ P 〈 0.05）. Probucol treatment prevented the atherosclerotic lesion development in both C57BL/6J and apoE^-/- mice. Compared with HFHC groups, the aorta lesions were significantly decreased by61.1% in C57BL/6J mice andby27.2% in apo E^-/- mice （P〈0.05）, respectively, after treatment ofprobucol. Admi-nistrafion of probucol lowered the serum levels of MDA and oxLDL, and elevated the levels of serum T-AOC and SOD. The restilts also demonstrated a more significant increase of PON1 activity and expression level in C57BL/6J mice than in aim E^-/- mice. Conclusion Probucol decreases the levels of serum lipids and alleviates the

关 键 词：病理学与病理生理学 载脂蛋白E基因缺陷小鼠 高脂血症 丙丁酚 氧化应激 对氧磷酶1 

分 类 号：R363[医药卫生—病理学]