脑脉通对骨髓干细胞动员保护大鼠脑缺血损伤的影响

Effect of Naomaitong on the protection of bone marrow stem cells on mobilization against injury in rats with cerebral ischemia

目的研究脑脉通对脑缺血大鼠骨髓干细胞动员(BMSCs)在血液和脑组织的变化及脑保护作用的影响。方法大鼠随机分为假手术组、模型组、脑脉通组、动员组、脑脉通+动员组,线栓法制备MCAO动物模型。皮下注射人重组粒细胞集落刺激因子(rG-CSF);脑脉通灌胃用药。检测大鼠外周血WBC及CD34+、脑组织CD34+变化;观察神经功能和脑组织病理改变;测定脑组织含水量和脑梗死面积。结果模型组大鼠外周血WBC(8.07±1.27)×109/L和CD34+细胞(3.17±0.75)个/μl增加,3d达到峰值,各治疗组增加更为明显;联合组2和3d外周血WBC、各时间点CD34+细胞均较动员组增加。各模型组大鼠脑组织CD34+表达增强,7d达到峰值(33.04±2.62)个/μl;各联合组较动员组增强明显。各模型组大鼠神经评分降低、脑含水量增加、脑梗死面积增大、脑组织病理损伤明显,以7d显著;动员组大鼠7和14d的上述指标改善;各联合组较动员组的改善明显。结论血液WBC数CD34+计数,脑组织、CD34+表达均显著显示,脑缺血可引起BMSCs进入外周血并向脑组织归巢,峰值时间存在差异;G-CSF可使BMSCs分布增加;脑脉通使动员后血液和脑组织BMSCs增多、脑组织峰值时间延长,且使其脑保护作用增强。

Objective To explore the effect of Naomaitong on mobilization of bone marrow stem cells （BMSCs） in blood and brain tissue and the role in protecting brain in rats with cerebral ischemia. Methods Rats were randomly divided into different groups. Middle cerebral artery occlusion （MCAO） model was duplicated with nylon thread. Rats in groups of mobilization and model were administrated with rG-CSF（ 10 ug^-1·d^-1） through subcutaneous injection before 3 d and after 2 d of operation respectively, once a day. Naomaitong was used through intragastric administration. On 2, 3, 7 and 14 d atier operation, rats blood were laken through abdominal aorta, then white blood cells （WBCs） and CD34＋ cells in peripheral blood were determined. Expression of CD34 ＋ cells in rats brain tissue were detected. Rats state, ratio of weight change and general neural iunction score （GNFS） and brain pathologic change were observed, and then rats brain water ratio （BWR） and cerebral infarction size （CIS） were measured. Results Rats mortality increased after operation and the decreases of weight on 7 d were more obvious. Compared to model groups, decreases of weight in treat groups abated. WBCs （ 8.07 ± 1.27） and CD34 ＋ cells （3.17 ± 0. 75 ） in peripheral blood in model group increased obviously and showed the highest level on 3 d after operation. Increases of WBCs and CD34 ＋ cells in rats of treat groups were more obvious. In comparison with that of mobilization groups, rats WBCs on 2 and 3 d combination groups increased more significantly and CD34 ＋ cells in each combination group were more higher. Expression of CD34 ＋ cells in brain of rats in model groups increased and showed the highest level on 7 d （ 33.04 ± 2.62 ） and the changes showed more obvious in each mobilization and combination group, especially in each combination group. Rats GNFS were lower in each model groups and BWR, CIS and brain pathologic increased obviously, especially on 7 d model group. The changes aboved improved significantly on 7 and 14 d mobilization groups. Compared to the changes in mobilization groups, the improvement in each combination group showed more obvious. Conclusions BMSCs could enter peripheral blood and move towards brain tissue after cerebral isehemia and the peak is different, rG-CSF could make BM- SCs increase both in peripheral blood and brain. Meanwhile, Naomaitong could increase BMSCs which are mobilized and make the peak of BMSCs in brain prolong, as well as enhance the protection against brain injury after cerebral ischemia.