红景天甙对间歇性低压低氧诱导的ApoE^(-/-)小鼠动脉粥样硬化的影响  

Effect of Salidroside on Atherosclerosis of ApoE^(-/-) Mice with Intermittent Hypobaric Hypoxia

作　　者：张立平[1] 郑曦[2] 马双陶[1] 杨大春[1] 李德[1] 王强[1] 张彦[1] 杨永健[1] 

机构地区：[1]成都军区总医院心内科,四川省成都市610083 [2]泸州医学院第一附属医院心内科,四川省泸州市646000

出　　处：《中国动脉硬化杂志》2014年第7期675-679,共5页Chinese Journal of Arteriosclerosis

基　　金：中国人民解放军成都军区总医院科研课题(2011YG-B32)

摘　　要：目的观察红景天甙对间歇性低压低氧诱导的载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化的影响及其可能机制。方法 30只8周龄健康雄性ApoE-/-小鼠随机分为常压常氧组、间歇性低压低氧组、低压低氧+红景天甙组,其中间歇性低压低氧组和低压低氧+红景天甙组被放置在模拟海拔5000 m低压低氧舱内每天8h,每组给予相同的普通饮食喂养,低压低氧+红景天甙组灌服红景天甙30 mg/(kg·d),而常压常氧组和间歇性低压低氧组灌服等量蒸馏水,连续灌胃12周后取小鼠血样测空腹血糖和血脂,取小鼠主动脉根部,HE染色观察动脉粥样硬化斑块的大小,Masson染色观察斑块内胶原含量,Western blot检测基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)和组织型基质金属蛋白酶抑制剂2(TIMP-2)蛋白的表达。结果三组空腹血糖和血脂水平无统计学差异(P>0.05);与常压常氧组比较,间歇性低压低氧组动脉粥样硬化斑块面积明显增加(P<0.01),胶原含量明显减少(P<0.01);与间歇性低压低氧组比较,低压低氧+红景天甙组斑块面积、MMP-2和MMP-9蛋白水平明显降低(P<0.01),而斑块内胶原含量、TIMP-2蛋白水平明显增加(P<0.01)。结论红景天甙能抑制间歇性低压低氧诱导的动脉粥样硬化斑块形成,并提高斑块的稳定性,其机制可能与红景天甙增加斑块内胶原含量有关。Aim To observe the effect of salidroside on atherosclerosis of apolipoprotein E gene knockout mice（ApoE- /-） with intermittent hypobaric hypoxia,so as to illuminate the role of salidroside on atherogenesis. Methods Thirty eight-week-old male ApoE- /-mice were randomized into normobaric normoxic group（ control group）,intermittent hypobaric hypoxia group（IHH）,hypobaric hypoxia ＋ salidroside group（intervention group） for 12 weeks. Mice in IHH group and intervention group were exposed to a hypobaric chamber mimicking the hypobaric hypoxia condition on an altitude of 5000 m for 8 hours every day,each group was fed with the same general diet,the intervention group was given salidroside 30 mg /（kg·d）,oral gavage,while the control group and IHH group were administered distilled water. Then fasting blood glucose（FBG） and plasma lipid levels were measured,paraffin sections of mice aorta roots were made. The aorta atherosclerotic lesion area and plaque collagen content were meassured by HE staining and Masson staining. Matrix metalloproteinase-2（MMP-2） and MMP-9,tissue inhibitor of metalloproteinase-2（ TIMP-2） protein expression were analyzed by Western blot. Results The three groups did not statisticly differ in FBG and plasma lipid levels（ P 〉 0. 05）.Compared with control group,atherosclerotic plaque area were increased significantly（P 〈 0. 01）,whereas plaque collagen content were increased in IHH group（P 〈 0. 01）. Compared with IHH group,plaque area and the protein expression of MMP-2 and MMP-9 were decreased significantly（P 〈 0. 01）,whereas plaque collagen content and the protein expression of TIMP-2 were increased in salidroside intervention group（ P 〈 0. 01）. Conclusion Salidroside attenuates atherosclerosis and enhances plaque stability in ApoE- /-mice of IHH. The mechanism is in connection with salidroside increased plaque collagen content.

关 键 词：红景天甙 低压低氧 载脂蛋白E基因敲除小鼠 动脉粥样硬化 斑块稳定性 

分 类 号：R363[医药卫生—病理学]