通心络超微粉对猪急性心肌梗死后移植骨髓间充质干细胞的影响

目的探讨通心络超微粉能否改善猪急性心肌梗死(AMI)局部微环境,从而提高移植自体骨髓间充质干细胞(MSCs)在体存活和移植效果。方法28头中华小型猪被分为4组(n=7),分别为对照、通心络超微粉(自AMI前3 d用药直至后4 d)、MSCs移植和通心络超微粉+MSCs联合组。AMI模型由阻断冠状动脉左前降支90 min制成,再灌注后即刻经心肌内注射DAPI标记的自体骨髓MSCs(3×107cells/动物)。在移植后1周(基线)和6周(终点),以核磁共振(MRI)检测心功能。6周后处死动物,检测移植细胞在体存活和分化、梗死周边心肌凋亡和氧化应激指标。结果终点时,与对照组、MSCs组和通心络超微粉组相比,联合组纤维化和炎症细胞浸润显著减轻,并伴较多存活心肌。与MSCs移植组相比,联合组移植细胞的在体存活和成心肌分化能力均显著增强(P<0.0001)。MRI显示在基线时各心功能参数无显著差异(P>0.05);终点时,和对照组相比,仅联合组左室射血分数(LVEF)显著增加(P<0.0001),室壁运动障碍节段数、梗死室壁增厚率、梗死面积和左室质量指数均显著减小(P<0.0001)。终点时,和对照组相比,在通心络超微粉组和联合组梗死周边区的心肌凋亡均显著减轻(P<0.0001),SOD显著增加(P<0.05),MDA显著减少(P<0.05)。结论实验表明AMI再灌注后即刻心肌内移植自体骨髓MSCs生存和分化能力有限,未产生显著功能学获益。而围移植期使用通心络超微粉可显著改善梗死局部微环境,提高移植细胞存活和分化,并产生显著心功能获益。

Effects of Micro-particle tongxinluo treatment around transplantation of mesenchymal stem cells on post-infarction swine hearts

Objective To investigate whether micro-particle Tongxinluo (MP-TXL) treatment can improve the survival and functional effects of implanted mesenehymal stem cells (MSCs) in post-infarct swine hearts.Methods Twenty eight Chinese mini-pigs were divided into four groups (n=7 in every group), including group control, group 2 (MP-TXL), group 3 (MSCs alone) and group 4 (MP-TXL+ MSCs), and then autologous bone marrow MSCs (3×10~7 cell/animal) were injected into postinfarct myocardium immediately after AMI.The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis.Cardiac function was detected at baseline (1 week after AMI) and endpoint (6 weeks after AMI).The apoptosis and oxidative stress level were investigated in the post-infarct myocardium at endpoint.Results At endpoint, there were less fibrosis and inflammatory cell infiltration in group 4 with more surviving myocardium than group control, and the potential of survival and differentiation of implanted MSCs was significantly more than that in group 3 (P<0.0001).Cardiac function was improved and the area of perfusion defect significantly decreased only in group 4 compared with control group (P< 0.0001 ).TUNEL assay indicated that MP-TXL treatment significantly decreased cellular apoptosis in peri-infarct myoeardium in group 2 and 4.Furthermore, the activity of superoxide dismutase (SOD) significantly increased, and malondialdehyde (MDA) decreased in the infarcted region decreased in group 2 and 4.Conclusions Our study demonstrated that based on MP-TXL-facilitation, improved the survival and differentiation potential of implanted MSCs after AMI accompanied by functional benefits, probably via anti-inflammation, anti-oxidative stress and anti-apoptosis effects of MP-TXL.