骨髓间充质干细胞植入改善心肌病心衰的实验研究

Mesechymal stem cells transplantation can improve function in doxorubicin- induced heart failure of rats

目的采用 5 aza 2’ deoxycytidine(5 aza CdR)诱导的MSCs移植于阿霉素心肌病心衰大鼠心肌中 ,评价其存活及对心功能的保护作用。方法体外培养Wistar大鼠的MSCs,用 0 .3μmol/L的 5 aza CdR体外两次诱导第 2代MSCs,然后将其用溴氮胞苷(BrdU)标记后植入阿霉素造模成全心衰心肌病大鼠的心肌中 ,同时以注射无血清培养基 (DMEM)的实验动物为对照组。移植后4周 ,通过心脏射血分数 (EF)等超声指标 ,研究其对心功能的保护作用 ;另外通过免疫组化研究细胞存活情况。结果移植后 4周 ,MSCs移植组大鼠的EF为 (95 .2± 3.7) % (n =9) ,DMEM移植对照组的EF为 (79.9± 6 .0 ) % (n =11) ,两组之间有显著性差异(P <0 .0 1) ;MSCs移植大鼠移植前后对照 ,心功能有改善 (P <0 .0 1,移植前EF =82 .3%± 6 .4 % )。移植的MSCs在心肌中存活 ,在 9只大鼠中均发现BrdU(+)细胞。结论经 5 aza CdR诱导的MSCs移植后 4周 ,能在阿霉素心肌病大鼠心肌中存活 ,并能改善心肌病全心衰大鼠的心功能。

Objective To investigate the survival of 5-aza-2-deoxycytidine (5-aza-CdR) induced MSCs in myocardium and their effects on global heart failure of rats induced by doxorubicin administration. Methods Wistar rat MSCs were cultured in vitro and the second passage MSCs were incubated together with 5-aza-CdR(0.3μmol/L) for two times. Then the induced MSCs labeled with bromodeoxyuridine(BrdU) were transplanted into the myocardium of rats in the model of global heart failure induced by means of doxorubicin admistration. The rats receiving serum-free medium injection were used as controls. Four weeks after transplantation, the parameters of heart function, such as ejection fraction (EF), were examined by echocardiography and the survival of transplanted MSCs were observed by immunohistochemistry. Results Four weeks after transplantation, the EF value of MSCs transplantation group and DMEM transplantation group were (95.2±3.7)%(n=9), and (79.9±6.0)%(n=11), respectively (P< 0.01). The heart function of MSCs transplantation group rats after transplantation was also improved (P< 0.01, EF=(82.3±6.4)% before transplantation). Transplanted cells could be identified by BrdU (+) cells(in all 9 rats). Conclusion Four weeks after transplantation, 5-aza-CdR induced MSCs could survive in the doxorubicin-treated hearts and improve the function in global heart failure cardiomyopathy rats.