组织工程心肌补片对黑山羊陈旧性心肌梗死心功能和建立侧支循环的影响

目的探讨自体骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)-小肠黏膜下层(sm a llin testina l subm ucosa,S IS)构建的组织工程心肌补片,移植于陈旧性心肌梗死区后对心功能及缺血区建立侧支循环的影响。方法将已建立急性心肌梗死模型后6周的黑山羊16只,随机分为实验组和对照组,实验组抽取自体骨髓,经体外分离M SC s,进行培养、传代,以第3代细胞行5-B rdU标记并与S IS支架材料复合培养5 d,制备M SC s-S IS组织工程心肌补片。将其缝合至陈旧性心肌梗死区;对照组仅行假手术处理。于植入后6周,采用超声心动图观察两组动物心功能变化,数字减影血管造影选择性左冠状动脉造影观察缺血心肌侧支循环的建立。结果术后6周实验组及对照组:心博出量、左心室射血分数分别为42.81±4.91、37.06±4.75 m l和59.20%±5.41%和44.56%±4.23%,组间差异均有统计学意义(P<0.05);左心室舒张末期容积、左室收缩末期容积分别为72.55±8.13、83.31±8.61 m l和29.75±5.98、46.25±6.68 m l,组间差异均有统计学意义(P<0.05);左心室舒张功能各项指标分别为:E峰最大速度分别为54.85±6.35 cm/s和43.14±4.81cm/s(P<0.01);A峰最大速度分别为52.33±6.65 cm/s和56.91±6.34 cm/s(P>0.05)。超声心动图显示对照组左室腔扩张明显,室壁运动明显减弱,梗死区呈瘤样扩张,局部室壁反常运动;实验组左室腔明显小于对照组,室壁运动较对照组强,心尖梗死区扩张不明显。选择性左冠状动脉造影见实验组左冠状动脉前降支远端与回旋支间明显侧支循环建立。结论M SC s-S IS构建的组织工程心肌补片移植于黑山羊陈旧性心肌梗死区后侧支循环建立,心功能有明显改善作用。

EFFECTS OF BONE MARROW MESENCHYMAL STEM CELLS ENRICHED BY SMALL INTESTINAL SUBMUCOSAL FILMS ON CARDIAC FUNCTION AND COMPENSATORY CIRCULATION AFTER MYOCARCADIAL INFARCTION IN GOATS

OBJECTIVE: To investigate effects of the autologous bone mesenchymal stem cells (MSCs) enriched by the small intestinal submucosa (SIS) film implantation on the myocardial structure, cardiac function, and compensatory circulation after myocardial infarction in the goats. METHODS: Sixteen black goats were selected and divided randomly into the control group (n= 8)and the experimental group (n= 8). The chronic myocardial infarction models were made by the ligation of the far end of the left anterior descending coronary artery. At the same time, MSCs were aspired from the thigh bone of the goats in the experimental group. MSCs were isolated by the centrifugation through a percoll step gradient and purified by the plating culture and depletion of the non-adherent cells. Primary MSCs were cultured in the DMEM medium supplemented with the fetal bovine serum in vitro. After that, the cultures were labeled by 5- BrdU. The active cells were transplanted into the SIS film. Six weeks after the ligation, the MSCs-SIS film was implanted by its being sutured onto the infarction area; whereas, the control group underwent a sham-operation. In both groups, echocardiographic measurements were performed before infarction, 6 weeks after infarction and 6 weeks after the MSC-collagen implantion, respectively, to assess the myocardial structure and cardiac function. The left coronary artery angiography was performed with the digital subtraction angiography. RESULTS: In an assessment of the left ventricular function, at 6 weeks after operation, the stroke volume and the ejection fraction of the control group and the experimental group were 42.81+/-4.91, 37. 06+/-4.75 ml and 59.20%+/-5.41%, 44.56% +/-4.23%, respectively (P<0.05). The end-disatolic volume and the end-systolic volume of the control group and the experimental group were 72.55+/-8.13, 83.31+/-8.61 ml and 29.75+/-5. 98, 46.25+/-6.68 ml, respectively (P<0. 05). The maximal velocity of peak E of contral group and experimental group were 54. 85+/-6.35 cm/s and 43.14+/-4.81cm/s (P<0. 01); and the maximal velocity of peak A of control group and experimental grouop were 52.33+/-6.65 cm/s and 56.91+/-6.34 cm/s (P>0. 05). Echocowdiography showing a distinctly dilatation of left ventricle with the ventricular dyskinesia in contral group, but without the ventricular dyskinesia in experimental group. The selective-coronary evngiography revealed that the obvious compensatory circulation established between the anterior descending branch and the left circumflex branch in the experimental group. CONCLUSION: Implantation of the autologus MSCs enriched by the SIS film can prevent dilatation of the left ventricular chamber and can improve the contractile ability of the myocardium, cardiac function, and collateral perfusion.