红景天甙对低压低氧诱导的ApoE-/-小鼠动脉粥样硬化斑块稳定性的影响

Effects of salidroside on atherosclerotic plaque stability in apolipoprotein E gene knock-out mice with hypobaric hypoxia

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-/-)小鼠动脉粥样硬化斑块稳定性的影响。方法:30只8周龄健康雄性ApoE-/-小鼠随机分为常压常氧组(对照组)、间歇性低压低氧组(低压低氧组)、低压低氧+红景天甙组(干预组),其中低压低氧组和干预组被放置在模拟海拔5 000m低压低氧舱内每天8h,每组给予相同的普通饮食喂养,干预组灌服红景天甙30mg·kg-1·d-1,而对照组和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及血脂,取小鼠主动脉根部的主动脉,Masson染色观察动脉粥样硬化斑块的大小及斑块内的胶原纤维含量,免疫组织化学染色检测基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶组织抑制剂-2(TIMP-2)蛋白的表达情况。结果:3组空腹血糖和血脂水平差异无统计学意义;与对照组比较,低压低氧组的动脉粥样硬化斑块面积明显增加,胶原含量明显减少(均P<0.01);与低压低氧组比较,红景天甙干预组斑块面积及MMP-2、MMP-9蛋白水平明显降低,而斑块胶原含量及TIMP-2蛋白水平明显增加(均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和降低MMP-2、MMP-9,提高TIMP-2蛋白的表达有关。

Objective：To observe the effects of salidroside on atherosclerotic plaque stability in apolipoprotein E gene knock-out（ApoE-/-）mice with intermittent hypobaric hypoxia.Method：Thirty eight-week-old male ApoE-/-mice were randomized into normal group（control group）,intermittent hypobaric hypoxia group（IHH group）,hypobaric hypoxia＋salidroside group（intervention group）for 12 weeks.Mice in IHH group and intervention group were exposed to a hypobaric chamer mimicking the hypobaric hypoxia condition on an altitude of 5 000mfor8 hours every day.Each group was fed with same general diet,the intervention group（salidroside 30mg·kg^-1·d^-1 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 masson staining.MMP-2,MMP-9and TIMP-2protein expressions were analyzed by immunohistochemistry staining.Result：The three group mice did not statistics differ in FBG and plasma lipid levels.Compared with control group,atherosclerotic plaque area were increased significantly,whereas plaque collagen content were increased in IHH group（both P〈0.01）.Compared with IHH group,plaque area and the protein expression of MMP-2 and MMP-9 were decreased significantly,whereas plaque collagen content and the protein expression of TIMP-2were increased in salidroside intervention group（all 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 and TIMP-2,MMP-2and MMP-9were decreased.