摘要
背景:金属蛋白酶组织抑制因子1可能通过抑制基质金属蛋白酶活性降低干细胞侵袭能力,提高其归巢修复能力。目的:观察转染金属蛋白酶组织抑制因子1基因骨髓间充质干细胞移植修复损伤心肌的能力。方法:开胸结扎SD大鼠冠状动脉前降支建立心肌梗死模型,1周后随机分组:空白组经尾静脉内注射DMEM悬液;干细胞组经尾静脉内注射含1×107骨髓间充质干细胞的DMEM悬液;绿色荧光蛋白-干细胞组经尾静脉内注射转染带有绿色荧光蛋白基因慢病毒空载体的骨髓间充质干细胞(1×107)DMEM悬液;TIMP-1-shRNA-干细胞组经尾静脉内注射转染TIMP-1-shRNA的骨髓间充质干细胞(1×107)DMEM悬液。结果与结论:造模后,4组大鼠心脏功能受损,收缩能力下降,治疗4周后心脏功能均有不同程度改善:与空白组比较,干细胞组、绿色荧光蛋白-干细胞组、TIMP-1-shRNA-干细胞组心脏收缩功能明显提高(P<0.05),心肌梗死面积百分比明显缩小(P<0.05),梗死区毛细血管密度明显增加(P<0.05),且TIMP-1-shRNA-干细胞组改善程度优于干细胞组、绿色荧光蛋白-干细胞组(P<0.05)。说明转染金属蛋白酶组织抑制因子1基因的骨髓间充质干细胞移植能够明显改善损伤心肌功能,修复缺血性心肌病。
BACKGROUND：Tissue inhibitor of metalloproteinase-1（TIMP-1） can decrease the invasion of stem cells by inhibiting metalloproteinase activity and thereby increase the number of homing stem cells.OBJECTIVE：To investigate whether intravenously injected bone marrow mesenchymal stem cells（BMSCs） can improve cardiac function in a rat myocardial infarction model.METHODS：Myocardial infarction model was induced by occluding the anterior descending coronary artery in 56 SD rats.One week later,myocardial infarction models were assigned to four groups.Rats in the control,BMSCs,green fluorescent protein-BMSCs and TIMP-1-shRNA-BMSCs groups received DMEM,DMEM containing 1×10 7 BMSCs,DMEM containing 1×10 7 BMSCs transfected with green fluorescent protein gene lentiviral empty vector and DMEM containing 1×10 7 BMSCs transfected with TIMP-1-shRNA,respectively via the tail vein.RESULTS AND CONCLUSION：After myocardial infarction induction,cardiac function was damaged and myocardial contractibility was decreased in each group.After treatment for 4 weeks,cardiac function improved to different extents.Compared with control group,rat myocardial contractibility was significantly increased（P 0.05）,myocardial infarction area was significantly reduced（P 0.05）,capillary density in the infarct area was significantly increased（P 0.05） in the BMSCs,green fluorescent protein-BMSCs and TIMP-1-shRNA-BMSCs groups,and the improvement was better in the TIMP-1-shRNA-BMSCs group than in the BMSCs and green fluorescent protein-BMSCs groups（P 0.05）.These results suggest that transplantation of BMSCs transfected by TIMP-1 gene can greatly improve rat myocardial function and thereforecon be used for treatment of ischemic cardiomyopathy.
出处
《中国组织工程研究》
CAS
CSCD
2012年第36期6724-6729,共6页
Chinese Journal of Tissue Engineering Research
