间歇性低氧通过上调脂蛋白相关磷脂酶A2和氧化型低密度脂蛋白表达促进动脉粥样硬化形成
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Intermittent Hypoxia Promote the Formation of Atherosclerosis by Increasing Expression of Lipoprotein-Associated Phospholipase A2 and Oxidized Low Density Lipoprotein
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    目的研究间歇性低氧及高脂饮食通过上调脂蛋白相关磷脂酶A2(Lp-PLA2)、氧化型低密度脂蛋白(ox-LDL)的表达促进动脉粥样硬化的形成。方法采用随机对照、前瞻性动物实验和析因设计的方法,建立间歇性低氧和高脂饮食兔动物模型,将24只4月龄新西兰大耳白兔随机分为四组:对照组、间歇性低氧组(IH组)、高脂饮食组(HFD组)和间歇性低氧+高脂饮食组(IH+HFD组),每组6只。IH组和IH+HFD组置于间歇性低氧舱中,每天8 h,每循环5 min,舱内最低氧浓度8%,最高氧浓度21%,HFD组和IH+HFD组给予高脂饲料饲养,间歇性低氧和高脂饮食干预12周,利用酶联免疫吸附法测定间歇性低氧和高脂饮食干预0、4、8和12周血浆中Lp-PLA2和ox-LDL含量的变化,在实验终点12周取主动脉弓和腹主动脉观察动脉粥样硬化的形成情况。结果在第8周和12周时,IH组、HFD组和IH+HFD组Lp-PLA2含量较对照组和第4周时升高(p<0.05);在第4、8和12周时IH+HFD组Lp-PLA2含量分别较对照组、IH组和HFD组升高(p<0.05);间歇性低氧和高脂饮食分别在第4、8和12周对Lp-PLA2的影响存在交互效应(p=0.000,p=0.001,p=0.000)。在第4、8和12周时,IH组、HFD组和IH+HFD组ox-LDL含量较对照组均升高(p<0.05),在第4周时明显高于第8周和12周(p<0.05);在第4、8和12周时IH+HFD组ox-LDL含量分别较对照组、IH组和HFD组升高(p<0.05);间歇性低氧和高脂饮食在第4周时对ox-LDL的影响存在交互效应(p=0.000),在第8周和12周时不存在交互效应(p=0.104和p=0.166)。间歇性低氧和高脂饮食干预下腹主动脉油红“O”染色及主动脉弓和腹主动脉组织HE染色后可观察到动脉粥样硬化的形成。结论间歇性低氧和高脂饮食可能通过上调血浆中Lp-PLA2和ox-LDL表达促进动脉粥样硬化形成。

    Abstract:

    AimTo investigate the intermittent hypoxia and high-fat diet promoting the formation of atherosclerosis through increasing expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) and oxidized low density lipoprotein (ox-LDL).MethodsUsing randomized controlled study, prospective animal and factorial experiment, the animal models were established by intermittent hypoxia and high-fat diet.24 New-Zealand white rabbits (4 months old) were divided into the following 4 groups: control group, intermittent hypoxia group(IH), high-fat-feeding group(HFD) and intermittent hypoxia & high-fat-feeding group (IH+HFD).Each group had 6 rabbits.Rabbits in IH group and IH+HFD group were placed in a cabin which nitrogen and air were periodically infused every 5 minutes for 8 h/day.The lowest level of oxygen concentration was at 8%.The highest level of oxygen concentration was at 21%.The HFD group and IH+HFD group were fed with fat-rich-stoyer.The intervention experiment lasted for 12 weeks.Blood samples for measurements of Lp-PLA2 and ox-LDL were collected at 0 w, 4 w, 8 w and 12 w.The formation of atherosclerosis in the aortic arch and abdominal aorta was observed.ResultThe Lp-PLA2 level of IH group, HFD group and IH+HFD group at 8th and 12th week was higher than control group and at 4th week, the difference has statistic significance (p<0.05).The Lp-PLA2 level of IH+HFD group at 4th, 8th and 12th week was higher than control group, IH group and HFD group(p<0.05).The two factors of IH and HFD had significant synergistic effects on the Lp-PLA2 at 4th, 8th and 12th week(p=0.000,p=0.001,p=0.000).The ox-LDL level of IH group, HFD group and IH+HFD group at 4th, 8th and 12th week was higher than control group(p<0.05).It was higher at 4th week than at 8th and 12th week (p<0.05).The ox-LDL level of IH+HFD group at 4th, 8th and 12th week was higher than control group, IH group and HFD group(p<0.05).The two factors of IH and HFD had significant synergistic effects on the ox-LDL at 4th week(p=0.000), however they had no significant synergistic effects at 8th and 12th week(p=0.104 and p=0.166).The formation of atherosclerosis was observed by oil red "O" staining in abdominal aortic and by HE staining in aortic arch and abdominal aorta under IH and HFD intervention.ConclusionThe intermittent hypoxia and high-fat diet can promote the formation of atherosclerosis through increasing expression of Lp-PLA2 and ox-LDL.

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李月春,刘国荣,王宝军,郝喜娃,张京芬,庞江霞,闫洁.间歇性低氧通过上调脂蛋白相关磷脂酶A2和氧化型低密度脂蛋白表达促进动脉粥样硬化形成[J].中国动脉硬化杂志,2012,20(9):792~796.

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  • 收稿日期:2011-10-14
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