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

作　　者：黄曾艳 黄曼萍[3] 彭春丽 刘永源[3] 李春燕 梁东辉[1] HUANG Zeng-yan;HUANG Man-ping;PENG Chun-li;LIU Yong-yuan;LI Chunyan;LIANG Dong-hui(School of Chinese Medicine,Southern Medical University,Guangzhou 510515,China;The First Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Zhujiang Hospital of Southern Medical Universi-ty,Guangzhou 510280,China;Maoming People's Hospital,Maoming 525000,China)

机构地区：[1]南方医科大学中医药学院,广东广州510515 [2]广州中医药大学第一附属医院,广东广州510405 [3]南方医科大学珠江医院,广东广州510280 [4]茂名市人民医院,广东茂名525000

出　　处：《中国病理生理杂志》2021年第1期34-40,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81774036)。

摘　　要：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.

关 键 词：动脉粥样硬化 情志刺激 基质细胞衍生因子1 CXC趋化因子受体4 

分 类 号：R541.1[医药卫生—心血管疾病] R363.2[医药卫生—内科学]