通心络对猪急性心肌缺血再灌注晚期微血管内皮屏障损伤的治疗作用  

Effect of Tongxinluo on microvascular endothelial barrier injury swine after acute myocardial ischemia-reperfusion

作　　者：张海涛[1] 康晟[2] 王春玥[1] 李向东[1] 韩硕龙 贾振华 杨跃进[1] ZHANG Haitao;KANG Sheng;WANG Chunyue;LI Xiangdong;HAN Shuolong;JIA Zhenhua;YANG Yuejin(Fuwai Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China;不详)

机构地区：[1]中国医学科学院北京协和医学院阜外医院,北京100037 [2]上海同济大学东方医院 [3]络病研究与创新中药国家重点实验室

出　　处：《山东医药》2020年第28期33-36,共4页Shandong Medical Journal

基　　金：国家重点研发计划中医药现代化研究重点专项(2017YFC1700503)。

摘　　要：目的探讨通心络灌胃对猪急性心肌梗死(AMI)再灌注晚期(第7天)微血管内皮屏障损伤的治疗作用。方法将40只中华小型猪,随机分为假手术组、模型组及低、中、高剂量组,每组8只。除假手术组外其他各组经冠脉前降支阻断90 min,再灌注120 min建立AMI再灌注模型,假手术组只穿管不阻断冠脉。低、中、高剂量组于冠脉阻断前90 min分别给予0.2、0.4、0.8 g/kg通心络灌胃1次,自第2天开始,分别给予0.1、0.2、0.4 g/kg通心络,每天喂食给药,共治疗7 d。分别于冠脉阻断前、阻断90 min、再灌注120 min及再灌注1、3、7 d采用ELISA法检测血清内皮素1(ET-1)、血管性血友病因子(vWF)。缺血再灌注后第7天,麻醉猪,取梗死区、边缘区和正常区心肌组织,用原位杂交技术检测各心肌组织中内皮细胞一氧化氮合酶(eNOS)、血管内皮细胞钙黏蛋白(VE-cadherin)mRNA表达,用Western blotting法检测各心肌组织中eNOS、VE-cadherin蛋白表达。结果与假手术组比较,模型组在冠脉阻断后血清ET-1、vWF水平高(P均<0.05),至再灌注7 d,血清ET-1水平回落,但仍高于假手术组(P<0.05)。与模型组比较,高剂量组在冠脉阻断90 min、再灌注120 min及再灌注1、3 d血清ET-1水平低(P均<0.05),而血清vWF水平则在以上各时间点及再灌注7 d均低(P均<0.05)。与假手术组比较,再灌注7 d模型组梗死区eNOS mRNA阳性表达率低(P<0.05),梗死区及梗死边缘区Ve-cadherin mRNA阳性表达率低(P均<0.05);与模型组比较,低、中、高剂量组各区心肌组织中eNOS、VE-cadherin mRNA阳性表达率随剂量增加逐渐升高,但组间比较差异均无统计学意义(P均>0.05)。与模型组比较,低、中、高剂量组各区心肌组织中eNOS、VE-cadherin蛋白表达随剂量增加逐渐升高,其中各通心络组梗死区及中、高剂量组边缘区eNOS蛋白表达、高剂量组梗死区VE-cadherin蛋白表达均高(P均<0.05)。结论通心络灌胃可减轻猪AMI再灌注�Objective To evaluate the sustained therapy of intragastric administration of Tongxinluo on microvascular endothelial barrier injury swine after the late-stage of acute myocardial infarction(AMI)-reperfusion.Methods Forty swine were randomly divided into the sham operation group,control group,low-dose(0.1 g/kg),medium-dose(0.2 g/kg)and high-dose(0.4 g/kg)groups.The AMI and reperfusion model was established by 90 min occlusion of left anterior descending,followed by 120 min reperfusion.No coronary artery was blocked in the sham operation group.Tongxinluo was administrated with double routine dosage before coronary occlusion and with routine dosage from the next day till the seventh day,which was 0.1,0.2,and 0.4 g/kg,respectively.The serum levels of endothelin-1(ET-1)and von Willebrand Factor(vWF)were detected by ELISA.Pathologic myocardial tissues were collected seven days after acute ischemia and reperfusion.The mRNA and protein expression levels of endothelial nitric oxide synthase(eNOS)and vascular endothelial cadherin(VE-cadherin)were detected by in situ hybridization(ISH)and Western blotting.Results Compared with the sham operation group,the serum ET-1 and vWF increased significantly after coronary occlusion in the control group.On the 7th day of reperfusion,both ET-1 and vWF were restored,but vWF was still significantly higher than that in the sham operation group.Compared with the control group,the serum ET-1 of the high-dose group significantly decreased at 90 min of coronary occlusion,at 120 min,1 and 3 days of reperfusion,while vWF decreased at all check points.Compared with the sham operation group,the positive expression of eNOS and VE-cadherin mRNA of infarcted area significantly decreased in the other groups on the 7th day of reperfusion,as well as the eNOS,but VE-cadherin significantly decreased only in the control,low-dose and medium-dose groups.Compared with the control group,Tongxinluo increased both mRNA and protein expression of eNOS and VE-cadherin,which was more significantly effective in the

关 键 词：急性心肌梗死 再灌注 微血管内皮屏障损伤 无复流 通心络 猪 

分 类 号：R542.2[医药卫生—心血管疾病]