调节“脑中血海”法联合骨髓间充质干细胞移植对大鼠缺血脑组织血管再生的影响

Effects of Chinese medicine for regulating "sea of blood in brain" combined with bone marrow stromal stem cell transplantation on angiogenesis in ischemic brain tissue of rats

目的:研究调节"脑中血海"中药脑脉1号联合骨髓间充质干细胞(bone marrow stromal stem cell,BMSC)移植对脑缺血再灌注大鼠血管再生和神经功能的影响。方法:制作大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,分为模型组、脑脉1号组、BMSC移植组、脑脉1号加BMSC移植治疗组,另选8只大鼠行假手术作为假手术组。分别于造模3、7、14d后进行神经行为学评分(behavior rating scale,BRS),观察脑组织病理损伤,免疫组织化学法检测血管内皮细胞标志物CD31的表达量。结果:与模型组相比,BMSC移植、脑脉1号以及二者联合治疗对大鼠BRS有显著改善(P=0.000),但在该指标上两者无交互效应。与模型组相比,BMSC移植、脑脉1号以及二者联合可显著增加CD31表达(P=0.000),且两者联合使用存在交互效应,与观察时点存在交互效应(P<0.01)。结论:调节"脑中血海"的中药脑脉1号可促进接受BMSC移植治疗的局灶性脑缺血大鼠的血管再生,改善BRS,随着疗程的延长,效果更加显著。

Objective： To observe whether Naomai Yihao （NM） Capsule, a compound traditional Chinese herbal medicine for regulating the ＂sea of blood in brain＂, and bone marrow stromal stem cell （BMSC） transplantation could improve angiogenesis in focal cerebral ischemia in rats. Methods： A rat model of middle cerebral artery occlusion （MCAO） was established. The rats were divided into untreated group, NM group, BMSC group and combination of NM and BMSC group （combined treatment group）. Another 8 normal rats were selected as sham-operated group. After 3-, 7- and 14-day reperfusion, behavioral rating scale （BRS） of the rats and histopathology of the cerebral tissue were evaluated. Expression of CD31 in the brain tissue was also measured by immunohistochemical method. Results. Compared with the untreated group, BRSs of the NM group, BMSC group and combined treatment group were decreased significantly （P=0. 000）, but there was no interacting effect between NM and BMSC transplantation. Compared with the untreated group, the numbers of CD31 positive cells in NM group, BMSC group and combined treatment group were increased significantly （P= 0. 000）, and there were interacting effects among NM, BMSC transplantation, and the observation time （P〈0.01）. After 14-day reperfusion, combination of NM and BMSC transplantation could largely increase the number of CD31 positive cells. Conclusion： NM is able to promote the angiogenesis and neurological impairment improvement in focal cerebral ischemia of rats which are administered with BMSC transplantation, and the effect is reinforced with the extension of treatment time.