情志刺激加速小鼠动脉硬化进展与SDF-1/CXCR4失衡的相关性研究

Correlation between progression of atherosclerosis accelerated by emo⁃tional stimulation and imbalance of SDF-1/CXCR4 in mice

目的:通过观察情志刺激对载脂蛋白E基因敲除(ApoE^(−/−))小鼠血浆、血小板、主动脉、海马及骨髓组织中基质细胞衍生因子1(SDF-1)和CXC趋化因子受体4(CXCR4)表达的影响,揭示情志刺激加重动脉粥样硬化斑块易损性的可能机制。方法:30只8周龄雄性ApoE^(−/−)小鼠随机分为正常对照组、高脂组和情志刺激模型组,每组10只,另取10只8周龄近交系C57BL/6J小鼠作为空白对照组。各组干预12周后取材,采用ELISA法检测小鼠血浆SDF-1和CXCR4含量,观察主动脉病理损伤程度,Western blot法检测各组小鼠血小板、主动脉、海马及骨髓中SDF-1和CXCR4的表达情况。结果:与空白对照组、正常对照组和高脂组比较,慢性不可预知温和应激(CUMS)情志刺激模型组小鼠主动脉中油红O染色显示动脉粥样硬化程度明显加重,血浆SDF-1和CXCR4含量显著增加(P<0.05),免疫组化可见主动脉组织SDF-1和CXCR4的平均吸光度显著升高(P<0.05)。Western blot检测结果显示,CUMS情志刺激模型组小鼠血小板、主动脉和海马中SDF-1和CXCR4的表达量显著增加(P<0.05),骨髓中SDF-1和CXCR4的表达量显著降低(P<0.05)。结论:SDF-1/CXCR4表达失调可能是情志刺激加速动脉粥样硬化进展的关键靶点通路。

AIM:To observe effects of emotional stimulation on expression of stromal cell-derived factor-1(SDF-1)and CXC chemokine receptor 4(CXCR4)in plasma,platelets,aortas,hippocampus and bone marrow of apolipoprotein E gene knockout(ApoE^(−/−))mice,and to reveal the possible mechanism of the aggravated atherosclerotic plaque vulnerability by emotional stimulation.METHODS:Thirty 8-week-old male ApoE^(−/−)mice were randomly divided into normal control group,high fat group,and emotional stimulation group.Ten 8-week-old inbred C57BL/6J mice served as blank control group.After 12 weeks of intervention,the serum levels of SDF-1 and CXCR4 were investigated by ELISA.The protein levels of SDF-1 and CXCR4 in platelets,aortas,hippocampus and bone marrow were determined by Western blot.The pathological damage of aortas was observed by oil red O staining.RESULTS:Compared with blank control group,normal control group and high fat group,the mice subjected to emotional stimulation showed more serious atherosclerosis in aortas detected by oil red O staining,and increased levels of SDF-1 and CXCR4 in the plasma and aortas were also observed(P<0.05).The results of Western blot showed that the protein levels of SDF-1 and CXCR4 in platelets,aortas and hippocampus were increased in the mice subjected emotional stimulation,but the expression of SDF-1 and CXCR4 in the bone marrow was decreased(P<0.05).CONCLUSION:Imbalance of SDF-1/CXCR4 may be the key target by which emotional stimulation accelerates the progression of atherosclerosis.