红景天甙对低压低氧诱导的ApoE^(-/-)小鼠动脉粥样硬化斑块及MMP-2、MMP-9和TIMP-2表达的影响

Effects of salidroside on atherosclerotic plaque and expressions of MMP-2, MMP-9 and TIMP-2 in ApoE^(-/-) mice with hypobaric hypoxia

目的:观察红景天甙对低压低氧诱导的载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化(AS)斑块及基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-2(TIMP-2)表达的影响。方法:30只8周龄Apo E-/-小鼠随机分为常压常氧组、低压低氧组、红景天甙组,后两组每天处于低压低氧状态,红景天甙组每天灌服红景天甙30mg/kg。12周后测空腹血糖及血脂,取小鼠主动脉根部的主动脉,masson染色观察AS斑块的大小及斑块内胶原含量,Western blot及血清检测MMP-2、MMP-9、TIMP-2蛋白表达。结果:3组空腹血糖和血脂无统计学差异;与常压常氧组比较,低压低氧组AS斑块面积明显增加(P<0.01),胶原含量明显减少(P<0.01);与低压低氧组比较,红景天甙组斑块面积及MMP-2,MMP-9蛋白明显降低(P<0.01),而斑块胶原含量及TIMP-2蛋白明显增加(P<0.01)。结论:红景天甙能抑制低压低氧诱导的AS斑块形成,并提高斑块稳定性,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蛋白表达有关。

Objective： To observe the effects of salidroside on atherosclerotic plaque and expression of matrix metalloproteinase-2 （MMP-2）, MMP-9, tissue inhibitors of metalloproteinase-2 （T1MP-2） in apolipoprotein E gene knock-out mice （ApoE^-/-） with hypobaric hypoxia. Methods： Thirty eight-week-old ApoE^-/- mice were randomized into normal group, intermittent hypobaric hypoxia （IHH） group, hypobaric hypoxia＋salidroside group. ApoE^-/- mice, except in the normal group, were in hypobaric and hypoxia enviroment, mice in hypobaric hypoxia＋salidroside group were given a gavage Of 30mg/kg salidroside for 12 weeks. Then fasting blood glucose （FBG） and plasma lipid levels were measured, and paraffin sections of mice aorta roots were made. The aorta atherosclerotic lesion area and plaque collagen content were meassured by Masson staining. Protein expression of MMP-2, MMP-9 and TIMP-2 was analyzed by Enzyme-linked immunosorbent assay （ELISA） and Western blot. Results： The three group mice did not statistically differ in FBG and plasma lipid levels. Compared with normal group, atherosclerotic plaque area was increased significantly （P〈0.01）, whereas plaque collagen content was decreased 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 that salidroside increased plaque collagen content and TIMP-2, MMP-2 and MMP-9 were decreased.