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目的通过高胆固醇血症诱发的小鼠动脉粥样硬化模型,对游离胆固醇通过激活未折叠蛋白反应诱导巨噬细胞凋亡的信号途径进行研究。方法C57BL6/J背景野生型和apoE基因缺陷小鼠各6只,分别使用普通饲料和高脂饲料分别喂养,13周后对两组动物的血脂分析,原位TUNEL染色观察巨噬细胞凋亡,并比较两组动脉组织中CHOP的蛋白表达。结果高脂饲料喂养的apoE基因缺陷小鼠血脂水平显著高于对照组,尤以胆固醇的升高最为明显,并形成了严重的动脉粥样硬化;TUNEL染色显示动脉粥样病灶中有大量的巨噬细胞凋亡;免疫印迹实验表明动脉粥样硬化的组织中CHOP表达显著增高。结论大量的游离胆固醇在巨噬细胞内聚集并通过激活未折叠蛋白反应诱导巨噬细胞凋亡,促进粥样斑块的形成。
OBJECTIVE: To study the signal pathway of macrophage apoptosis induced by free cholesterol through activation of unfolded proteins through the model of atherosclerosis in mice induced by hypercholesterolemia. Methods Six C57BL6 / J mice with wild-type and apoE-deficient mice were fed with normal diet and high-fat diet respectively. After 13 weeks, the blood lipid of the two groups were analyzed. TUNEL staining was used to observe the apoptosis of macrophages. The protein expression of CHOP in two groups of arteries was compared. Results The apoE gene-deficient mice fed with high-fat diet had significantly higher blood lipid levels, especially cholesterol, which led to severe atherosclerosis. TUNEL staining showed a large number of atherosclerotic lesions Apoptosis; Western blotting showed that CHOP expression was significantly increased in atherosclerotic tissues. Conclusion A large amount of free cholesterol accumulates in macrophages and induces the apoptosis of macrophages through the activation of unfolded proteins and promotes the formation of atherosclerotic plaque.