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目的:观察ApoE~(-/-)小鼠动脉粥样硬化发生过程中microRNA-146a(miR-146a)的变化,探讨miR-146a与动脉粥样硬化之间的关系。方法:在ApoE~(-/-)小鼠中通过高脂高胆固醇喂饲构建动脉粥样硬化模型,分别在喂饲后第0周、4周、8周、12周、16周时采血和分离主动脉组织,通过HE染色和油红O染色观察主动脉组织的斑块形态,计算主动脉内膜/中膜比值和主动脉斑块的脂质含量;采用Real-Time PCR检测第0周、4周、8周、12周、16周时血浆和主动脉组织的miR-146a水平。结果:在高脂高胆固醇饲养后第8周时ApoE~(-/-)小鼠主动脉组织开始出现动脉粥样硬化,在第16周时主动脉粥样硬化最显著,16周时主动脉组织的内膜/中膜比值和主动脉斑块的脂质含量显著升高(P<0.01);在动脉粥样硬化发生过程中,小鼠血浆和主动脉组织中的miR-146a水平均明显升高,其中血浆miR-146a的峰值出现在第8周(P<0.01),之后血浆miR-146a逐渐下降;而主动脉组织的miR-146a水平从第4周开始升高(P<0.05),逐渐上升至16周时达到峰值(P<0.01);主动脉组织中miR-146a水平与ApoE~(-/-)小鼠主动脉粥样硬化呈强正相关性(r=0.892 5,P<0.000 1)。结论:miR-146a可能参与了ApoE~(-/-)小鼠主动脉主动脉粥样硬化的发生。
Objective: To observe the changes of microRNA-146a (miR-146a) during the development of atherosclerosis in ApoE ~ (- / -) mice and to explore the relationship between miR-146a and atherosclerosis. Methods: Atherosclerosis model was established by feeding high fat and high cholesterol in ApoE ~ (- / -) mice. Blood samples were collected at 0, 4, 8, 12 and 16 weeks after feeding Aortic tissue was isolated and plaque morphology was observed by HE staining and oil red O staining to calculate aortic intima / media ratio and aortic plaque lipid content; Real-Time PCR was used to detect the 0th week , 4 weeks, 8 weeks, 12 weeks, 16 weeks of plasma and aortic tissue miR-146a levels. RESULTS: ApoE ~ (- / -) mice began to show atherosclerosis in the aortic tissue at the 8th week after feeding with high-fat and high cholesterol. The aortic atherosclerosis was the most significant at the 16th week. The ratio of intima to media and the lipid content of aortic plaques were significantly increased (P <0.01). During the process of atherosclerosis, the levels of miR-146a in plasma and aorta of mice were significantly higher (P <0.01), then the plasma miR-146a gradually decreased; while the aortic tissue miR-146a levels increased from the 4th week (P <0.05) , Peaked at 16 weeks (P <0.01). The level of miR-146a in aorta tissue was positively correlated with atherosclerosis in ApoE ~ (- / -) mice (r = 0.892 5, P <0.000 1). Conclusion: miR-146a may be involved in the development of aortic aorta in ApoE ~ (- / -) mice.