地黄低聚糖联合脂肪组织来源干细胞移植治疗小型猪急性心肌梗死的疗效

摘要

目的探讨地黄低聚糖（RGOs）联合同种异体脂肪组织来源干细胞（ASCs）移植治疗小型猪急性心肌梗死（AMI）的疗效及其可能的机制。方法经皮球囊封堵冠状动脉左前降支制备小型猪AMI模型（n＝17），随机分为4组：对照组（n＝5），RGOs组（n＝4），ASCs组（A组，n＝4）及RGOs＋ASCs联合治疗组（n＝4）。RGOs组及联合治疗组造模前3天及造模后1月饲以RGOs粗提物（4 g，2次／天）；造模1周后（7～10 d）经冠状动脉移植同种异体ASCs（0．8×106 kg－1），对照组及RGOs组注入0．9％氯化钠注射溶液。移植后8周，延迟增强核磁共振扫描（DE-MRI）评价各组心脏结构及功能变化，荧光显微镜及激光共聚焦扫描观察ASCs存活及分化，免疫组织化学法观察梗死区微血管密度，Masson三色染色法评价梗死区纤维化程度。结果与对照组比较，联合治疗组可以明显改善左心室功能，增加梗死区室壁厚度，减小左心室质量指数及梗死体积（均P＜0．05）。病理和免疫组织化学结果显示，联合治疗组ASCs的存活多于ASCs组（P＜0．01），并表达心肌细胞标记物（cTnT、α-actin）及血管标志物（vWF、α-SMA）。联合治疗组梗死区微血管密度明显高于其他3组（P＜0．01）。与对照组比较，ASCs组以及联合治疗组均能明显降低梗死区纤维化程度（P＜0．05，P＜0．01）。结论 RGOs可以提高ASCs移植治疗小型猪AMI疗效，改善心功能，减轻左心室重构，其作用机制可能与RGOs促进ASCs增殖分化，抗纤维化有关。%Objective To explore the efficacy and potential mechanisms of Rehmannia Glutinosa Oligosaccha-rides (RGOs)combined with allogenic adipose tissue-derived stem cells (ASCs)transplantation for acute myocardial infarction (AMI)of miniswine.Methods AMI models were performed by occlusion of the left anterior descending cor-onary artery.A total of 17 miniswines survived after AMI were divided into four groups:control group(n=5 ),treated with saline;RGOs group (n=4),ASCs group(n=4)and RGOs+ASCs group (n=4).RGOs and RGOs+ASCs group were administration crude extract of RGOs from 3 days prior to AMI to one month post AMI (4g,two times per day).ASCs (0.8 ×106 kg-1 )were delivered by intracoronary one week later (7 to 10 days post-AMI).Left ventricu-lar function,scar size,and transmural extension will be assessed by delayed-enhanced magnetic resonance imaging at baseline and after 8 weeks post cell transplantation.The infarct area and implanted cells were histologically studied.Re-sults The combination therapy improve left ventricular ejection fraction,increased wall thickness of myocardial infarc-tion,reduced left ventricular mass index and infarct size compared with control group(all P<0.05).ASCs survival was significantly better in combined group than that in ASCs group (P<0.01),and the markers of the cardiomyocytes(cTnT and α-actin)and vessel(vWF and α-SMA)were detected.The microvessel density in combination group was signifi-cantly higher than that in the others three groups(P<0.01).Combination therapy can reduce fibrosis of myocardial in-farction in ASCs and in combination group compared with control group (P<0.05 and P<0.01 respectively).Conclu-sion The RGOs+ASCs combination therapy can enhance the effect of ASCs in the treatment of AMI,improve cardiac function and prevent ventricular remodeling.The mechanism may be related to RGOs in promoting the proliferation,sur-vivals of ASCs and the anti-fibrosis effect.