补阳还五汤对急性心肌梗死大鼠移植骨髓间充质干细胞归巢作用的实验研究

An experimental study on homing effects of the Buyang Huanwu decoction on transplanted BMSCs in rats with acute myocardial infarction

目的:观察补阳还五汤对急性心肌梗死大鼠移植骨髓间充质干细胞(Bone Mesenchymal Stem Cells,BMSCs)归巢的影响及补阳还五汤与BMSCs联合对心肌损伤的防护作用。方法:取7~8周龄SPF级Sprague-Dawley(SD)大鼠48只,雌雄各半,体质量(220±20)g,随机分为4组:假手术组、模型组、BMSCs移植组、补阳还五汤+BMSCs移植组。各组大鼠灌胃3 d后随机取6只采集血清,采用生化法检测心肌酶[磷酸肌酸同工酶(CK-MB)、肌钙蛋白I(Cardiac Troponin I,cTnI)]水平;采用酶联免疫吸附试验(ELISA)检测炎症因子白细胞介素(Interleukin,IL)-6、肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)表达情况;取心肌梗死及边缘区心肌组织,镜下观察移植BMSCs归巢情况。其余大鼠继续灌胃,4周后运用多普勒超声心动图分析心功能变化。结果:与模型组比较,补阳还五汤+BMSCs移植组CK-MB、cTnI含量降低明显,差异有显著统计学意义(P <0.01)。与模型组、BMSCs移植组比较,补阳还五汤+BMSCs移植组IL-6、TNF-α水平下降,差异有统计学意义(P <0.05)。荧光显微镜下示补阳还五汤+BMSCs移植组的荧光细胞表达数量高于单纯BMSCs移植组(P <0.05)。与模型组比较,补阳还五汤+BMSCs移植组左室射血分数升高明显,差异有统计学意义(P <0.05)。结论:补阳还五汤可以促进移植BMSCs归巢,发挥心肌损伤的防护作用,其机制可能与补阳还五汤抑制心肌梗死后局部炎症、祛瘀生新、改善心肌局部代谢环境有关。

Objective:To observe the effect of the Buyang Huanwu decoction(补阳还五汤)on homing of transplanted bone Omesenchymal stem cells(BMSCs)in rats with acute myocardial infarction and the protective effect of the combination of the two on myocardial injury.Methods:A total of 48 SPF Sprague-Dawley(SD)rats with body weight(220±20)g at the age of 7 to 8 weeks were selected.They were randomly divided into 4 groups:blank group,model group,BMSCs transplantation group,Buyang Huanwu decoction+BMSCs transplantation group.After 3 days of intragastric administration,6 rats in each group were randomly collected for blood serum collection.The levels of myocardial enzymes(CK-MB,cTnI)were detected by biochemical method.The expression of inflammatory factor interleukin-6(IL-6)and tumor necrosis factor(TNF-α)were detected by ELISA.The homing of transplanted BMSCs was observed under microscope by taking myocardial tissue of myocardial infarction and marginal area.The cardiac function of the remaining rats was analyzed by Doppler echocardiography 4 weeks later.Results:Compared with model group,the contents of CK-MB and cTnI were decreased significantly in the Buyang Huanwu decoction+BMSCs transplantation group,and the difference was statistically significant(P<0.01).Compared with model group and BMSCs transplantation group,the levels of IL-6 and TNF-αin the Buyang Huanwu decoction+BMSCs transplantation group were decreased,and the difference was statistically significant(P<0.05).Fluorescence microscopy showed that the expression number of fluorescent cells in the Buyang Huanwu decoction+BMSCs transplantation group was higher than that in the BMSCs transplantation group alone(P<0.05).Compared with the model group,left ventricular ejection fraction in the Buyang Huanwu decoction+BMSCs transplantation group was significantly increased,and the difference was statistically significant(P<0.05).Conclusion:The Buyang Huanwu decoction can promote the homing of transplanted BMSCs and play a protective role in myocardial injury.The mechanism of the Buyang Huanwu decoction may be related to inhibiting local inflammation after myocardial infarction,removing blood stasis and generating new blood,and improving the local metabolic environment of myocardium.