E1A激活基因阻遏子在动脉粥样硬化血管中的表达及其与炎症因子的关系  

Expression of cellular repressor of E1A-stimulated genes in atherosclerotic artery and its relationship with inflammatory factors

作　　者：杨桂棠[1] 韩雅玲[1] 闫承慧[1] 

机构地区：[1]沈阳军区总医院心内科,辽宁沈阳110016

出　　处：《心脏杂志》2016年第1期7-10,24,共5页Chinese Heart Journal

基　　金：辽宁省博士启动基金资助(20131136)

摘　　要：目的探讨E1A激活基因阻遏子(CREG)在动脉粥样硬化(AS)血管中的表达及其与炎症因子的关系。方法 Apo E(-/-)小鼠6周龄断奶后给予高脂喂养。8周后取主动脉血管,采用HE染色观察血管的形态学变化;采用免疫荧光染色观察CREG、SMα-actin和巨噬细胞标志物Mac-3的表达变化。取高脂喂养的1~8周小鼠血管,采用Western blot方法检测AS血管中CREG及核转录因子(NF)-κB的表达的变化。结果在Apo E(-/-)小鼠高脂喂养8周,主动脉血管AS斑块明显形成,斑块内有胆固醇结晶,斑块凸凹不平,管腔明显狭窄。免疫荧光显示AS血管中,CREG表达明显下降,同时SMα-actin表达也下降,而Mac-3表达增高。Apo E(-/-)小鼠高脂喂养2~8周,取动脉血管行蛋白定量分析,结果显示高脂喂养2周时,CREG在动脉血管中的表达不是降低,而是明显升高,高脂喂养第4周,CREG表达急剧下降,而后又逐渐上升,但不能升至正常水平。同时NF-κB随着时间的推移,表达逐渐升高。结论在AS进程中,血管中膜的VSMCs由收缩表型向合成表型转化,细胞增生活跃、分化减弱,CREG作为维持VSMCs分化的蛋白,在血管中的表达与AS进展密切相关,同时伴随着炎症因子表达逐渐升高。AIM To investigate the effects of cellular repressor of E1A-stimulated genes （CREG） on atherosclerotic lesion formation and its relation with inflammatory factors. METHODS Immunofluores- eence and Western blot was used to detect the expression of CREG in atherosclerotie arteries. The mor- phology of the artery and expressions of CREG and smooth muscle ot-actin （SMc^-actin） on natural ather- osclerotic formation were observed in ApoE （-/-） knockout mice fed with high-fat diet. RESULTS From 1 to 8 weeks of atherogenic diet, CREG expression in arterial wall of ApoE （-/-） mice did not decrease at the early stage of AS. However, its expression obviously increased within 2 weeks of athero- genic diet. At the fourth week of atherogenic diet, CREG expression decreased rapidly and later increased gradually until the 8th week. But the expression of CREG did not reach the normal level. At the same time, the change of nuclear factor-kappa B （NF-KB） expression, an inflammatory marker, was observed in a time-dependent fashion. Within 8 weeks of atherogenic diet, NF-KB increased gradually, indicating that inflammation continued and became more serious throughout atherosclerosis. CONCLUSION The phe- notype of VSMCs changes from differentiation to synthesis in atherosclerotic formation. CREG expression decreases with the development of atherosclerosis, suggesting that CREG is associated with atherosclerosis and inflammation.

关 键 词：E1A激活基因阻遏子 动脉粥样硬化 血管平滑肌细胞 ApoE(-/-)小鼠 

分 类 号：R363[医药卫生—病理学]