复方丹参滴丸联合人脐血间充质干细胞移植对急性心肌梗死小鼠作用机制研究  

Mechanism Study of Compound Danshen Dripping Pills Combined with Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation on Acute Myocardial Infarction Mice

作　　者：赵吉玲 彭漪[1] 徐维芳[1] 余国龙[1] ZHAO Ji-ling;PENG Yi;XU Wei-fang;YU Guo-long(Department of Cardiology,Xiangya Hospital of Central Southern University,Changsha 410008)

机构地区：[1]中南大学湘雅医院心内科,长沙410008

出　　处：《中国中西医结合杂志》2021年第9期1093-1099,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金面上项目(No.81570266);湖南省自然科学基金重点项目(No.2015SK2025)。

摘　　要：目的观察复方丹参滴丸(CDDP)联合人脐血间充质干细胞(hUCB-MSCs)移植对急性心肌梗死(AMI)小鼠脾脏和外周血单核细胞M1/M2亚型转化、心肌炎症反应和心功能的影响。方法雄性Balb/C小鼠结扎冠状动脉左前降支,制备AMI模型。 32只造模成功小鼠随机分为4组,对照组、移植组、CDDP组和联合治疗组,每组8只。造模术后24 h,各组均接受生理盐水0.2 mL注射及0.2 mL灌胃,CDDP组将CDDP 270 mg/(kg·d)溶于灌胃生理盐水,移植组将1×106 hUCB-MSCs溶于注射生理盐水,联合治疗组接受两种治疗。治疗7 d后,每组随机选取5只小鼠行超声心动图检测心功能,HE染色观察心肌病理变化和心梗区白细胞计数,Masson染色观察胶原沉积情况,流式细胞仪检测外周血及脾脏单核细胞M1/M2比值,ELISA检测外周血IL-10水平。结果 HE染色结果显示各组小鼠梗死区均有不同程度心肌细胞丢失,由大量平行或交错的胶原纤维束组成,形成疤痕组织,可见白细胞浸润。与对照组比较,其余三组残存心肌细胞数量较多,白细胞浸润减少,三组左室射血分数(LVEF)、外周血IL-10水平升高(P<0.05),心梗区白细胞计数、胶原沉积比、脾脏和外周血单核细胞M1/M2比例降低(P<0.05)。与CDDP组比较,移植组心梗区白细胞计数增加,联合治疗组心梗区白细胞计数减少,移植组和联合治疗组LVEF、IL-10水平升高,外周血单核细胞M1/M2比例下降(均P<0.05)。与移植组比较,联合治疗组外周血单核细胞M1/M2比例下降(P<0.05)。结论 CDDP联合hUCB-MSCs移植治疗可促进AMI小鼠心外单核巨噬细胞M1/M2亚型转化,减低小鼠心肌梗死局灶炎症反应,并改善心功能,疗效优于单纯hUCB-MSCs移植。Objective To observe the effects of compound Danshen Dripping Pills(CDDP) combined with human umbilical cord blood mesenchymal stem cells(HUCB-MSCs) transplantation on transformation of M1/M2 subtypes in spleen and peripheral blood mononuclear cells,myocardial inflammation and cardiac function in mice with acute myocardial infarction(AMI).Methods Male Balb/C mice were used to establish AMI model by ligating the left anterior descending coronary artery.Thirty-two AMI mice were randomly divided into four groups:control group,CDDP group,transplantation group and combined treatment group,with 8 mice in each group.Twenty-four hours after operation,all groups received 0.2 mL normal saline by tail vein injection and 0.2 mL normal saline by gavage;270 mg CDDP dissolved in normal saline was gavaged per day in the CDDP group,1×106 of HUCBMCs dissolved in normal saline was injected via tail vein in the transplantation group,the combined treatment group received both treatment in CDDP group and transplantation group.After 7 days of treatment,5 mice in each group were randomly selected.Cardiac function was detected by echocardiography.Myocardial pathological changes and white blood cell(WBC) count in infarcted area were observed by hematoxylin-eosin(HE) staining.Collagen deposition was observed by Masson staining.The M1/M2 ratio in the peripheral blood and spleen was measured by flow cytometry.The leve of IL-10 in peripheral blood was measured by ELISA.Results HE staining showed that varying degrees of myocardial cells were lost in infarcted area of mice in each group,which was replaced by scar tissue composed of a large number of parallel or staggered collagen fiber bundles,and WBC infiltration was observed.Compared with the control group,the left ventricular ejection fraction(LVEF) and IL-10 level in peripheral blood increased(P<0.05),WBC count in infarcted area,collagen deposition ratio and M1/M2 ratio of spleen and peripheral blood mononuclear cells decreased in other three groups(P<0.05).Compared with CDDP group,WBC cou

关 键 词：复方丹参滴丸 人脐血间充质干细胞 急性心肌梗死 炎症反应 单核巨噬细胞M1/M2 

分 类 号：R542.22[医药卫生—心血管疾病]