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[冠状动脉内自体骨髓单个核细胞移植对犬心律失常的影响]

[Effect of intracoronary autologous bone marrow mononuclear cells transplantation on arrhythmia in canines].

作者信息

Tang J, Sun G Y, Chen T, Wang Y D, Zhang J, Qi X Q

机构信息

*The Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2016 Dec 24;44(12):1030-1035. doi: 10.3760/cma.j.issn.0253-3758.2016.12.008.

Abstract

To observe the survival and the differentiation of grafted bone marrow cells (BM-MNCs) in host myocardium. To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins, important mediator for arrhythmia genesis after myocardial infarction. Acute myocardial infarction (AMI) was induced by left anterior descending coronary artery (LAD) ligation in hybrid canine. BM-MNCs suspension was prepared by density centrifugation. The BM-MNCs were labeled with CM-DiI. Sixteen hybrid canines were randomly divided into transplantation group and control group. BM-MNCs (transplantation group, =10) or saline (control group, =6) were intracoronarily infused into infarction related artery at 2 hours after AMI. At 6 weeks after AMI, ventricular fibrillation (VF) was induced in infarct area and periinfarct area. The effective refractive period (ERP) of different areas in myocardium was assessed and the expression of connexin 43 (Cx43) was assessed by immunohistochemical staining. Six weeks after the BM-MNCs transplantation, CM-DiI labeled BM-MNCs were mainly located within periinfarct and infarct area. Some BM-MNCs were positive for Cx43. Combined" CM-DiI and FITC" in images were observed. VF was induced in 2 out of the 10 canines in transplantation group and in 2 out of the 6 canines in control group in infarct area. VF was not induced in periinfarct area of both groups. The ERP of infarct area ((85.0±9.3) ms vs. (90.0±7.1)ms, >0.05), periinfarct area (87.8±9.4 vs. 90.0±7.1, >0.05) and normal area (85.0±12.0 vs. 88.3±9.4, >0.05) was similar between transplantation group and control group. The expression of Cx43 in normal area was similar between transplantation group and control group (3 543.7±446.0 vs. 3 431.7±421.5, >0.05). The expression of Cx43 in periinfarct area of transplantation group was significantly higher than that in control group (2 312.5±412.0 vs. 1 356.2±332.7, <0.05), but was still much less than in normal area (2 312.5±412.0 vs. 3 543.7±446.0, <0.05). The expression of Cx43 in infarct area was similar between transplantation group and control group (327.0±98.7 vs. 311.3±78.7, >0.05). The implanted BM-MNCs could survive in the infarcted lesion and differentiate into cells expressing Cx43.In transplanted group, VF was not induced in periinfarct area. ERP of infarct area, periinfarct area and normal area is similar between two groups. The expression of Cx43 in periinfarct area was significantly higher in transplantation group than that in control group.

摘要

观察移植的骨髓单个核细胞(BM-MNCs)在宿主心肌中的存活及分化情况。观察BM-MNCs移植是否可能导致心律失常,以及BM-MNCs移植是否会改变连接蛋白的空间分布,连接蛋白是心肌梗死后心律失常发生的重要介质。通过结扎杂种犬左冠状动脉前降支诱导急性心肌梗死(AMI)。采用密度离心法制备BM-MNCs悬液。用CM-DiI标记BM-MNCs。16只杂种犬随机分为移植组和对照组。在AMI后2小时经冠状动脉向梗死相关动脉内注入BM-MNCs(移植组,n = 10)或生理盐水(对照组,n = 6)。AMI后6周,在梗死区和梗死周边区诱发室颤(VF)。评估心肌不同区域的有效不应期(ERP),并通过免疫组织化学染色评估连接蛋白43(Cx43)的表达。BM-MNCs移植6周后,CM-DiI标记的BM-MNCs主要位于梗死周边区和梗死区。部分BM-MNCs呈Cx43阳性。观察图像中“CM-DiI和FITC”的组合情况。移植组10只犬中有2只在梗死区诱发VF,对照组6只犬中有2只在梗死区诱发VF。两组梗死周边区均未诱发VF。移植组与对照组梗死区的ERP((85.0±9.3)毫秒对(90.0±7.1)毫秒,P>0.05)、梗死周边区的ERP(87.8±9.4对90.0±7.1,P>0.05)和正常区的ERP(85.0±12.0对88.3±9.4,P>0.05)相似。移植组与对照组正常区Cx43的表达相似(3543.7±446.0对3431.7±421.5,P>0.05)。移植组梗死周边区Cx43的表达明显高于对照组(2312.5±412.0对1356.2±332.7,P<0.05),但仍远低于正常区(2312.5±412.0对3543.7±446.0,P<0.05)。移植组与对照组梗死区Cx43的表达相似(327.0±98.7对311.3±78.7,P>0.05)。植入的BM-MNCs可在梗死灶内存活并分化为表达Cx43的细胞。在移植组,梗死周边区未诱发VF。两组梗死区、梗死周边区和正常区的ERP相似。移植组梗死周边区Cx43的表达明显高于对照组。

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