自体骨骼肌卫星细胞移植对MI大鼠心肌的治疗性血管新生作用

Role of Therapeutic Angiogenesis by Rat Auto-skeletal Muscle Satellite Cells Implanted into Infarction Myocardium

目的 了解自体骨骼肌卫星细胞移植对MI大鼠心肌的治疗性血管新生作用及其机制。方法 4 5只Wistar大鼠随机分为假手术组 (n =1 5 )、对照组 (n =1 5 )及移植组 (n =1 5 ) ,对照组及移植组大鼠经结扎冠状动脉前降支建立心肌梗死 (MI)模型。将体外培养 2周的移植组大鼠自体SC以注射的方式移植到梗死区周围 ,4周后病理观察移植细胞的生长、增殖情况 ,测定缺血心肌中VEGFmRNA、VEGF蛋白的表达情况及缺血心肌毛细血管密度的改变。结果 SC在梗死区中可增殖分化为横纹肌纤维。与假手术组及对照组相比 ,移植组缺血心肌中VEGFmRNA、VEGF蛋白的表达及毛细血管密度均明显增高 (P <0 0 1或 0 0 0 1 )。结论 SC在心肌梗死区中可增殖分化为横纹肌样细胞 ,并通过自分泌和旁分泌的方式增加缺血心肌VEGF的表达 。

Objective To investigate the role of therapeutic angiogenesis and its mechanisms by rat auto skeletal muscle satellite cells implanted into infarction myocardium.Methods Approximately 107～109 SCs were cultivated in vitro from Wistar rats whose left anterior descending(LAD) artery had been ligated to create a myocardial infarction(MI). Two weeks after MI, autologous SCs、serum free culture medium and 0.9% sodium chloride injection was injected into the scar tissue of transplantation(n=15)、control(n=15) and sham operation animals respectively. Four weeks after injection, the expression of VEGF protein and capillary density in the ischemic myocardium were demonstrated by immunohistochemical method, and the exptession of VEGF mRNA in the ischemic myocardium were detected by reverse transcription polymerase chain reaction(RT PCR).The diffrentiated myofibers from SCs in the infarcted site were observed by pathologic examination and immunohistochemical method.Results The SCs had progressively differentiated into striated muscle fibers in the myocardial infarction site, and immunohistochemical analysis comfirmed their skeletal muscle origin.Compared with the MI and sham operation group, the expression of VEGF mRNA and VEGF protein in the ischemic myocardium were markedly increased in the SC transplantation group( P <0.01, 0.001).There were no significant difference between the MI and sham operation group ( P >0.05). Compared with the SO group, capillary density in the ischemic myocardium was markedly increased in the MI and SC transplantation group( P <0.05, 0.001). Capillary density in the SC transplantation group was higher than that in the MI group( P <0.01).Conclusion The SCs, after being implanted into the myocardial infarction site, not only showed myocardial regeneration, but showed the ability to improve the expression of VEGF mRNA and VEGF protein in the ischemic myocardium and increase the capillary density in the ischemic myocardium.