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骨髓间质干细胞移植上调心肌梗死区Cx43表达并改善其分布
Mesenchymal stem cells transplantation upregulates Cx43 expression and improves its distribution in infarcted myocardium
【摘要】 目的探讨骨髓间质干细胞(MSCs)移植能否上调心肌梗死区缝隙连接蛋白43(connexin43,Cx43)的表达,改善缝隙连接(gapjunction,GJ)的分布。方法40只日本大白兔随机分为正常对照组(N组)、假手术组(SH组)、心肌梗死组(MI组)和MSCs组。开胸结扎冠状动脉左前降支制造心肌梗死模型,1h后将5-溴脱氧尿核苷(BrdU)标记的MSCs(MSCs组)或培养基(MI组)移植入心肌梗死区。术后6周取心脏标本,免疫组化法鉴定植入细胞、Cx43蛋白表达与GJ分布。结果免疫组化显示,MSCs组心肌梗死区可见BrdU阳性细胞;与正常心肌比较,MI组心肌梗死中心区及边缘区Cx43显著减少(P<0.01),GJ分布紊乱;与MI组比较,MSCs组心肌梗死边缘区Cx43表达增加(P<0.05),GJ分布紊乱改善;在梗死中心区未见明显变化。结论MI可以导致梗死中心区和边缘区Cx43蛋白水平表达下降,GJ分布混乱;同种异体MSCs移植能改善GJ分布的紊乱,上调边缘区Cx43蛋白的表达。MSCs移植有可能减少心肌梗死后心律失常的产生。
【Abstract】 Objective To investigate whether mesenchymal stem cells(MSCs)transplantation for myocardial infarction(MI)can modulate gap junction(GJ)distribution and upregulate Cx43 expression.Method 40 Japan rabbits were randomly divided into normal control group(N group),sham operation group(SH group),MI group and MSCs group.MI was created by ligation of the left anterior descending(LAD)coronary artery.Bromodeoxyuridine(BrdU)-labeled MSCs(MSCs group)or culture medium(MI group)were injected into the infarcted myocardium 1 hour after MI.Immunohistochemistry is for the evaluation of Cx43 protein and MSCs surviving in infarcted myocardium at 6th week after operation.Results Immunohistochemical stain revealed that BrdU-positive cells were seen in the infarcted myocardium in MSCs group.Compared with the normal myocardium,decrease of Cx43 inmmunolabelling(P<0.01)and disturbance of its distribution were seen in the scar and adjacent regions in MI group.In MSCs group,Cx43 positive GJ was significantly augmented(P<0.05)and its distribution was more regularity in periphery of the scar compared with MI group.That was not seen in the center of the scar.Conclusions MI can lead to decrease of Cx43 expression and disturbance of GJ distribution in the scar and adjacent regions.Exogenous MSCs transplantation can modulate disturbance of GJ distribution and upregulate Cx43 expression at the periphery of the scar.It should probably reduce arrhythmogenesis after MI.
【Key words】 Mesenchymal stem cells; Acute myocardial infarction; Cells transplantation; Gap junction; Connexin43;
- 【文献出处】 中国急救医学 ,Chinese Journal of Critical Care Medicine , 编辑部邮箱 ,2007年07期
- 【分类号】R542.22
- 【被引频次】7
- 【下载频次】130