麝香保心丸对ApoE^-/-小鼠心肌梗死后动脉粥样硬化进程和循环单核细胞亚群的影响  

Effect of Shexiang Baoxin Pill on Atherosclerosis and Circulating Monocyte Subsets in Atherosclerotic ApoE^-/-Mice after Myocardial Infarction

作　　者：陈羽斐 胡亮 张红旗[2] 贾剑国 施海明 罗心平 周国民[2] 范维琥 沈伟 CHEN Yu-fei;HU Liang;ZHANG Hong-qi;JIA Jian-guo;SHI Hai-ming;LUO Xin-ping;ZHOU Guo-min;FAN Wei-hu;SHEN Wei(Department of Cardiology,Huashan Hospital,Fudan University,Shanghai,200040;Department of Anatomy,Histology and Embryology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai,200032;Department of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,450052;Department of Cardiology,Zhongshan Hospital,Fudan University,Shanghai,200032)

机构地区：[1]复旦大学附属华山医院心内科,上海200040 [2]复旦大学上海医学院人体解剖与组织胚胎学系,上海200032 [3]郑州大学第一附属医院心血管内科,郑州450052 [4]复旦大学附属中山医院心内科,上海200032

出　　处：《中国中西医结合杂志》2020年第12期1478-1483,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金面上项目(No.81673701,No.81573710)。

摘　　要：目的观察麝香保心丸对载脂蛋白E基因敲除(ApoE^-/-)小鼠心肌梗死后动脉粥样硬化斑块进程和循环单核细胞亚群(CD11b^+Ly6G^-CD115+Ly6C^hi和CD11b^+Ly6G^-CD115+Ly6C^lo)的影响。方法35只6周龄雄性ApoE^-/-小鼠,高脂喂养10周,选择10只小鼠为假手术组(sham组,等量生理盐水灌胃),25只小鼠通过结扎左冠状动脉前降支建立心肌梗死模型,将造模成功的20只小鼠采用随机数字表法分为心肌梗死组(MI组,等量生理盐水)和麝香保心丸组[MI+SBP组,100 mg/(kg·d)],每组10只,持续灌胃4周。全自动生化仪检测小鼠血浆TC、TG和LDL-C水平,油红O染色检测主动脉全长斑块面积,F4/80免疫荧光染色检测主动脉窦斑块内巨噬细胞含量,流式细胞术分析循环单核细胞亚群比例。结果与sham组比较,MI组主动脉粥样硬化病变明显加重(P<0.01),斑块内巨噬细胞含量增加(P<0.01),单核细胞数量及Ly6C^hi单核细胞亚群数量明显增加(P<0.01)。与MI组比较,MI+SBP组主动脉粥样硬化病变明显改善(P<0.01),斑块中F4/80^+巨噬细胞含量减少(P<0.01),单核细胞数量及Ly6C^hi单核细胞亚群数量减少(P<0.05,P<0.01)。3组之间Ly6C^lo单核细胞亚群数量及TC、TG、LDL-C水平比较差异无统计学意义(P>0.05)。结论心肌梗死会加速动脉硬化病变进程,麝香保心丸通过减少循环中炎性单核细胞比例和斑块中巨噬细胞含量,调控动脉粥样硬化斑块的炎症反应,且不依赖于血脂水平的变化。Objective To evaluate the protective effect of Shexiang Baoxin Pill(SBP)on atherosclerotic de-velopment and the role of circulating monocyte subsets(CD11b^+Ly6G^-CD115+Ly6C^hi and CD11b^+Ly6GCD115+Ly6C^lo)in atherosclerotic ApoE^-/-mice after myocardial infarction(MI).Methods Thirty-five male ApoE^-/-mice at 6 weeks of age were fed with a high-fat diet for 10 weeks,10 mice recruited in a sham surgery group,administered with equal volume of normal saline by gastrogavage,and the other twenty-five mice received myocardial infarction surgery by ligating left anterior descending branch.Twenty successfully modeled mice with MI were randomly devided into MI group(equal volume of normal saline)and MI+SBP group(SBP,100 mg·kg^-1·d^-1)by random digit table,10 in each group.All mice were intervened for 4 weeks.TC,TG and LDL-C levels in plasma were measured enzymatically using an automatic analyzer.Aortic lesion areas were evaluated with oil red O staining.The macrophage in plaque of aortic sinus were analyzed by F4/80 immunofluorescence staining.Flow cytometry was used to explore the proportions of circulating monocyte subsets.Results Compared with the sham sur-gery group,aortic lesions were significantly aggravated(P<0.01),macrophage content in plaque was increased(P<0.01),the number of circulating monocytes and the inflammatory Ly6C^hi monocyte subset increased(P<0.01)in the MI group.Compared with the MI group,SBP treatment reduced aortic lesions(P<0.01),F4/80-posi-tive macrophages in plaque decreased(P<0.01),monocyte levels and Ly6C^hi monocyte subset levels decreased(P<0.05,P<0.01)in MI+SBP group.There was no statistical difference in Ly6C^lo monocyte subset or TC,TG and LDL-C levels among the three groups(P>0.05).Conclusions MI accelerated atherosclerosis progress.SBP had significantly anti-inflammatory effect in atherosclerosis by reducing the proportion of pro-inflammatory monocytes in circulation and the content of macrophages in plaques accompanied by no changes on plasma lipid profiles.

关 键 词：动脉粥样硬化 麝香保心丸 单核细胞亚群 炎症反应 

分 类 号：R285.5[医药卫生—中药学]