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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。
Objective To investigate the expression of E1A-activated gene repressor (CREG) in atherosclerosis (AS) blood vessels and its relationship with inflammatory cytokines. Methods Apo E (- / -) mice were fed a high fat diet after 6 weeks of weaning. The aortic vessels were taken after 8 weeks and the morphological changes of blood vessels were observed by HE staining. The expression of CREG, SMα-actin and macrophage marker Mac-3 were observed by immunofluorescence staining. The blood vessels of mice aged 1 to 8 weeks fed with high fat diet were used to detect the changes of CREG and NF-κB expression in AS blood vessels by Western blot. Results In Apo E (- / -) mice fed with high-fat diet for 8 weeks, AS plaques of aorta were obviously formed. Cholesterol crystallized in the plaque. The plaque was uneven and the lumen was stenosed. Immunofluorescence showed that the expression of CREG was significantly decreased in AS vessels, while the expression of SMα-actin was also decreased, while the expression of Mac-3 was increased. Apo E (- / -) mice were fed with high fat for 2 to 8 weeks. The quantitative analysis of arterial blood vessels protein showed that the expression of CREG in arterial blood vessels was not decreased but significantly increased at 2 weeks of high fat diet, During the fourth week of high fat diet, the expression of CREG decreased sharply and then gradually increased, but it could not rise to normal level. At the same time NF-κB gradually increased with time. CONCLUSIONS: In the process of AS, the VSMCs in the vascular membrane transform from the contractile phenotype to the synthetic phenotype, the cell proliferation is active and the differentiation is weakening. The expression of CREG, as a protein that maintains the differentiation of VSMCs, is closely related to the progression of AS, Inflammatory factor expression gradually increased.