骨髓间充质干细胞移植联合脑脉1号对大鼠缺血组织血管生成的影响

Effects of Bone Marrow Messchymal Stem cell Transplantaion Combined with Naomai Yihao on Angiogenesis in Cerebral Ischemic Tissue of Rat

目的研究骨髓间充质干细胞(BMSCs)移植联合调节"脑中血海"中药脑脉1号对大鼠脑缺血区后血管生成的影响及其机制。方法制作大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,随机分为3组,即模型组、BMSCs移植组、BMSCs移植联合脑脉1号组。于造模后7,14,21 d进行神经行为学评分,免疫组织化学染色检测脑缺血边缘区VEGF的表达,激光共聚焦显微镜观察血管生成情况。结果缺血后7,14,21 d,BMSCs移植组、联合治疗组神经功能较模型组均有较明显改善,联合治疗组改善均优于BMSCs移植组(P﹤0.05)。BMSCs移植组、联合治疗组VEGF阳性表达高于模型组(P<0.01),联合治疗组高于BMSCs移植组(P<0.05)。微血管直径、面积联合治疗组>BMSCs移植组>模型组,差异具有统计学意义(P﹤0.05)。结论 BMSCs移植联合脑脉1号促进缺血区血管生成和神经功能恢复的效果明显优于单纯BMSCs移植组,两者联用具有协同效应。促血管生成的机制可能与其上调VEGF的表达有关。

Objective To observe the effects of bone marrow messchymal stem cell transplantaion,with Naomai yihao（NM）,a compound traditional Chinese herbal medicine for regulating the＂sea of blood in brain＂on angiogenesis in cerebral ischemic tissue of rat. Methods A rat model of middle cerebral artery occlusion（MCAO） was established,and the rats were randomly divied into 3 groups：untreated group,BMSCs transplantation group,BMSCs transplantation＋NMYH group.After 7-,14-and 21-day reperfusion,behavioral rating scale（BRS） of the rats and expression of VEGF in the brain tissue were measured by immunohistochemical method.Laser scanning confocal microscopy（LSCM） was used to measure angiogenesis. Results On 7、14、21days after cerebral ischemia,the neurological function of the rats between BMSCs transplantation group and BMSCs transplantation＋NMYH group had significant recovery,the outcome of BMSCs transplantation＋NMYH group surpassed the BMSCs transplantation group＇s（P﹤0.05）.Compared with the model group,the numbers of VEGF positive cells in BMSCs transplantation group and BMSCs transplantation＋NMYH group were increased significantly（P﹤0.01）,the changes were better in BMSCs transplantation＋NMYH group than in BMSCs transplantation group（P﹤0.05）.Compared with the model group,diameter and area of microvessels significantly increased in all BMSCs transplantation group and BMSCs transplantation＋NMYH group（P0.05）,the changes were better in BMSCs transplantation＋NMYH group than in BMSCs transplantation group（P﹤0.05）. Conclusion The effect of improving the angiogenesis in boundary regions of ischemia and neurological function recovery in BMSCs transplantation＋NMYH group was significantly superior to BMSCs transplantation group.BMSCs transplantation combined with NMYH has synergistic effects.The mechanism of improving angiogenesis may be correlated to the up-regulation of expression of VEGF.