重庆医学2012，Vol.41Issue(11)：1096-1099,后插2,封3,6.DOI:10.3969/j.issn.1671-8348.2012.11.022
曲美他嗪联合骨髓间质干细胞移植治疗急性心肌梗死的实验研究
The experimental research on the treatment of acute myocardial infarction by trimetazidine and bone marrow mesenchymal stem cells transplantation
摘要
Abstract
Objective To investigate the effects of trimetazidine (TMZ) on the survival of mesenchymal stem cells (MSCs) in an ex-vitro model of hypoxia and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). Methods MSCs were cultured in serum-free medium and exposed to hypoxia for 12h with or without TMZ .The viability and apop-tosis of MSCs at passage 3 were examined by transmission electron microscope .Thirty wistar rats were divided randomly into 3 groups ,including AMI control group,MSCs transplantation group,and TMZ+MSCs group.MSCs were injected into peri-infarct myocardium (MSCs and TMZ+MSCs groups) thirty minutes after coronary artery ligation .The rats in TMZ+MSCs group were additionally fed TMZ from 3 days before AMI to 28 days after AMI .Cardiac structure and function were assessed by echocardio -graphy 28 days after transplantation .The survival and differentiation of transplanted cells were detected by immunofluorescent stai -ning .The cellular apoptosis in the peri-infarct region was detected with TUNEL assay .Blood samples were collected before the start of TMZ therapy and 24h ,48h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured .Results In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment .In vivo ,car-diac infarct size was significantly smaller ,cardiac function significantly improved in the MSCs and TMZ + MSCs groups than those in the control group .Combined treatment with TMZ and MSCs implantation demonstrated a further decrease in MSCs apoptosis ,a further increase in MSCs viability ,a further decrease in infarct size ,and a further improvement in cardiac function ,compared with those of MSCs group.The baseline levels of inflammatory cytokines (CRP,TNF-αt) were not significantly different among the groups .However ,all parameters at 24h were lower in TMZ+MSCs group than those in MSCs group .Conclusion Implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery .The inhibition of inflammatory cytokines expression may be the potential mechanism .关键词
曲美他嗪/骨髓间质干细胞/移植/心肌梗死Key words
trimetazidine/ bone marrow mesenchymal stem cells / transplantation /myocardial infarction引用本文复制引用
朱刚艳,徐红新,田毅浩,马红梅,唐世琪,汪福良,邬松林..曲美他嗪联合骨髓间质干细胞移植治疗急性心肌梗死的实验研究[J].重庆医学,2012,41(11):1096-1099,后插2,封3,6.基金项目
国家自然科学基金资助项目(30700314) （30700314）
湖北武汉市科技局资助项目(20065004116-02). （20065004116-02）
