人脐血单个核细胞多次静脉移植家兔急性心肌梗死后的胶原重构

背景：以往干细胞移植治疗心肌梗死的研究,均为单次经静脉或冠脉注射移植。目的：进一步验证人脐血单个核细胞多次静脉移植对家兔急性心肌梗死胶原重构及心功能影响。方法：取家兔45只结扎冠脉左前降支制备急性心肌梗死模型,随机分为3组,①多次移植组：造模后7,9,11,13d经耳缘静脉注入BrdU标记人脐血单个核细胞生理盐水。②单次移植组：造模后7d注入BrdU标记人脐血单个核细胞生理盐水,9,11,13d注入生理盐水。③心梗对照组：仅注入生理盐水。另取家兔5只为假手术组。结果与结论：与对照组相比,两移植组心功能左室短轴缩短率、左室射血分数明显升高（P〈0.05）;且多次移植组改善效果优于单次移植组（P〈0.05）;免疫组织化学显示两移植组造模后2,4周心梗周边区均存在BrdU阳性细胞,但多次移植组BrdU阳性细胞计数多于单次移植组;改良Masson’s染色显示与假手术组比较,对照组梗死区及非梗死区胶原密度显著增加,梗死区域胶原纤维部分融合,排列较紊乱,心肌基本组织结构破坏;与对照组比较,两移植组造模后2,4周梗死周边区域心肌细胞间胶原含量、胶原纤维明显减少,胶原纤维排列较为有序;与单次细胞移植组比较,多次细胞移植组进一步改善。提示多次静脉移植脐血单个核细胞改善急性心肌梗死心功能、阻抑心肌胶原纤维重构疗效优于单次静脉移植。

Effects of multi-intravenous transplantation of human cord blood mononuclear cells on the remodeling of cardiac collagen after myocardial infarction in rabbits

BACKGROUND：In previous studies,the treatment of myocardial infarction by using stem cell transplantation was done via single intravenous or coronary injection transplantation.OBJECTIVE：To investigate the effects of multi-intravenous transplantation of human cord blood mononuclear cells（HCBMCs） on the remodeling of cardiac collagen and heart function after myocardial infarction in rabbits.METHODS：Forty-five Chinese rabbits underwent ligation of the left anterior coronary artery for the preparation of myocardial infarction models.They were randomly divided into three groups.①Multi-transplantation group：They were intravenously injected with HCBMCs labeled with bromodexyuridine（BrdU） and normal saline at 7,9,11 and 13 days post-operation.②Single cell transplantation group：They were intravenously injected with HCBMCs labeled with BrdU at 7 days post-operation and normal saline at 9,11,and 13 days post-operation.③Control group：They were intravenously injected with normal saline at 7,9,11 and 13 days post-operation.In addition,five Chinese rabbits acted as the sham operation group.RESULTS AND CONCLUSION：Compared with the control group,left ventricular fractional shortening（LVFS） and left ventricular ejection fraction（LVEF） were improved significantly in the multi-transplantation group and single cell transplantation group（P 0.05）;while LVFS and LVEF were improved more significantly in the multi-transplantation group than in the single-transplantation group（P 0.05）;immunohistochemistry results demonstrated that BrdU positive cells were found in the peri-myocardial infarction area in the both transplanted groups at 2 and 4 weeks after the operation.Moreover,the number of BrdU positive cells in the multi-transplantation group was larger than that in the single-transplanted group.Masson＇s trichrome staining showed that compared with the sham operation group,the density of collagen fibers in the control group was significantly increased,and the collagen fibers were fused partially and arranged irregularly.Compared with the control group,the collagen and collagen fibers in both transplanted groups were decreased significantly,and the collagen fibers arranged more regularly after the operation.The multi-intravenous transplantation of HCBMCs for myocardial infarction is superior in improving cardiac function and inhibiting myocardial collagen remodeling,compared to single intravenously transplanted HCBMCs.