孤儿核受体Nur77参与AopE-/-小鼠颈动脉易损斑块的形成

Orphan receptor Nur77 participates in formation of vulnerable carotid atherosclerotic plaque in ApoE-/-mice

目的:研究孤儿核受体Nur77在AopE-/-小鼠动脉粥样硬化易损斑块形成中的作用。方法:AopE-/-小鼠左肾动脉和左颈总动脉联合部分结扎建立颈动脉易损斑块模型,采用HE染色观察斑块病理学改变,免疫荧光染色结合激光扫描共聚焦显微镜技术观察斑块中Nur77蛋白的表达。同时,体外培养小鼠巨噬细胞系RAW264.7,在氧化低密度脂蛋白(oxLDL)及其主要成分7-酮胆固醇(7-ketocholesterol,7-KC)或者游离胆固醇(FC),以及炎症介质(LPS、IL-1β)等条件刺激下,应用蛋白免疫印迹技术(Western blot)检测Nur77蛋白表达变化。结果:AopE-/-小鼠颈动脉易损斑块局部有Nur77蛋白高表达,而oxLDL及其组成成分(7-KC和FC)以及某些炎症介质(如LPS、IL-1β等)均能在RAW264.7细胞中诱导Nur77蛋白表达上调。结论:孤儿核受体Nur77可能在动脉粥样硬化易损斑块发展进程中发挥着重要作用。

AIM ： To investigate whether orphan receptor Nur77 is involved in the formation of vulnerable carotid atherosclerotic plaque in ApoE-/- mice. METHODS ： Using the method of partial ligation of left carotid and left renal arteries, we generated an ApoE-/- mouse model of vulnerable carotid atherosclerotic plaque. The pathological changes of atherosclerotic plaques were observed using H/E staining and the expression of Nur77 was detected by laser confocal microscopy after immunofluorescence staining. Macro- phages （ murine RAW 264.7 cells） were cultured and were stimulated with oxLDL and its main lipid components 7-ketocholesterol （7-KC） or free cholesterol （ FC ） and some inflammatory mediators （ LPS or IL-113）. The protein expression of Nur77 was detected by Western blotting. RESULTS ： Nur77 is highly expressed in vulnerable carotid atherosclerotic plaques in ApoE-/- mice. In addition, oxLDL and its main lipid components （7-KC or FC） and some inflammatory mediators （LPS or IL-113） induced the expres- sion of Nur77 in murine RAW 264.7 cells in vitro. CONCLUSION ： Orphan receptor Nur77 participates in the formation of vulnerable carotid atherosclerotic plaque in ApoE-/- mice.