SOCS蛋白的多重作用：SOCS1和SOCS3在动脉粥样硬化中的差异表达
Multipleroles of SOCS proteins: Differential expressions of SOCS1 and SOCS3 in atherosclerosis

摘要：目的 明确动脉粥样硬化(atherosclerosis, AS)进展中，细胞因子信号抑制物(SOCS)表达水平的变化及SOCS表达与胆固醇水平之间的关系。方法 使用载脂蛋白E基因敲除(ApoE-/-)小鼠，分别以高脂与正常饮食喂养，在不同年龄段检测其主动脉斑块中SOCS1和SOCS3的蛋白及mRNA表达水平；还采集18例无冠心病男性的外周静脉血，提取外周血单核细胞(PBMC)检测其SOCS1和SOCS3的mRNA表达水平。结果 在ApoE-/-小鼠中，SOCS1的表达先升高后下降，但高脂饮食组表达峰值前移；SOCS3的表达随喂养时间的增加而增加，该趋势在喂养高脂饮食组中更为明显；SOCS1/CD68和SOCS3/CD68的表达与高脂饮食持续时间增加呈相反的趋势；在高脂饮食喂养的ApoE-/-小鼠中，白细胞介素-6(IL-6)在主动脉中的表达也随着喂养时间的延长而增加；在无冠心病人群的PBMC中，血浆总胆固醇水平与SOCS3 mRNA表达水平呈正相关(r=0.433，P=0.012)。结论 SOCS1和SOCS3在AS中呈差异化表达，SOCS3与IL-6可能促进AS的发生与发展。
ABSTRACT: Objective? ?To illuminate the changes in expression of suppressor of cytokine signaling (SOCS) and the correlation between SOCS expression and cholesterol levels in atherosclerosis (AS). Methods? ?A mouse AS model was established in apolipoprotein-deficient (ApoE-/-) mice. The mice were fed either with a chow or high-fat diet. The mRNA and protein expressions of SOCS1 and SOCS3 in plaque and vessels were determined at different time points. Furthermore, SOCS1 and SOCS3 mRNA expressions were detected in the peripheral blood mononuclear cells (PBMCs) obtained from 18 male subjects with no coronary heart disease (non-CHD). Results? ?The expression of SOCS1 in the?ApoE-/- mice increased first and then decreased and the high-fat diet accelerated the appearance of the peak. The expression of SOCS3 increased with the increase of feeding duration, and this trend was more pronounced in the mice fed with high-fat diet. SOCS1/CD68 and SOCS3/CD68 showed the opposite trend in expression with the increased duration of high-fat diet. Interleukin-6 (IL-6) expression in the aorta of the?ApoE-/- mice fed with high-fat diet also increased with the increased feeding duration. In the non-CHD group, the total serum cholesterol level was positively correlated with SOCS3 mRNA expression in the PBMCs (r=0.433, P=0.012). Conclusion? ?These results demonstrate the differential expressions of SOCS1 and SOCS3 in AS and suggest that SOCS3, together with IL-6, may promote the formation and development of AS