活血化瘀药调控干细胞旁分泌效应修复损伤脑组织作用机制的研究  

Mechanism of stem cell paracrine effect on repairing damaged brain tissue regulated by drug for promoting blood circulation for removing blood stasis

作　　者：张宝霞[1] 张金生[2] 杜梅梅 汪萍[3] 

机构地区：[1]河南中医学院第一附属医院,郑州450008 [2]河南中医学院第三附属医院,郑州450000 [3]河南省肿瘤医院,郑州450000

出　　处：《中华中医药杂志》2015年第1期288-292,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：2010年河南省高校杰出科研人才创新工程--科技创新杰出青年项目(No.104100510010)~~

摘　　要：目的:探讨活血化瘀方药对干细胞旁分泌效应修复损伤脑组织的影响。方法:参照改良Zea-Longa法建立大鼠大脑中动脉脑缺血再灌注损伤模型(MCAO)。随机分为模型组,活血化瘀高、中、低剂量组;各组再随机按1、3、7、14、28d时点分为亚组,每亚组实验结束时仍有8只存活大鼠。免疫组化法检测不同时间点梗死边沿区CD105+-BMSC、PLGF、HIF-lα、Caspase-3、PARP表达情况;光学显微镜下观察不同时间点梗死边沿区病理变化。电镜下观察不同时间点MCAO梗死边沿区超微结构变化。结果:各个时间点活血化瘀高、中剂量组Ang-1、HIF-1α表达均高于活血化瘀低剂量组,且Ang-1、HIF-1α表达与CD105+-BMSC的表达相吻合,差异有统计学意义。模型组,活血化瘀低、中、高剂量组大鼠脑梗死边缘区Caspase-3、PARP阳性细胞在1d达到高峰,其后Caspase-3、PARP阳性细胞数逐渐降低。活血化瘀中、高剂量组与模型组相比时间点表达均降低。病理和超微结构显示活血化瘀高、中剂量组可不同程度的减轻MCAO大鼠脑组织的损害。结论:活血化瘀药通过影响干细胞的旁分泌效应,抑制脑缺血区神经细胞的凋亡,促进半暗区神经细胞的修复和血管再生达到治疗脑梗死的目的。Objective： To investigate the influence of drugs for promoting blood circulation for removing blood stasis on repairing damaged brain tissue by stem cell paracrine. Methods： Animal models of middle cerebral artery occlusion （MCAO） were established referring Zea-Longa method. Rats were randomly divided into four groups as model group and Chinese medicine groups （high, middle, low dosage group）, and rats of each group were divided into 5 subgroups according to time points as 1, 3, 7, 14, 28d. There were 8 rats in each subgroup at the end of the experiment. Immunohistochemistry was used to detect the expression of CD105^＋-BMSC, PLGF, HIF-1α, Caspase-3 and PARP in infarction edge area at different time points. The pathological and ultrastructural changes in infarction edge area at different time points were observed with optical microscope and electron mircroscope. Results： The expression of Ang-1 and HIF-1α of high and middle dosage of Chinese medicine groups at each time point was higher than that of low dosage of Chinese medicine group. The expressions of Ang-1, HIF-1α and CD105^＋-BMSC were coincident, and the difference was statistically significant. The positive cells of Caspase-3 and PARR in infarction edge area of rats in model group and Chinese medicine groups at its peak in the first day, then the number of positive cells gradually reduced. Compared with the model group, the time expression of middle and high dosage of Chinese medicine group both decreased. The results of pathology and ultrastructure showed that the high and middle dosage of drug for promoting blood circulation for removing blood stasis could reduce the damage of MCAO rat brain to varying degrees, Conclusion： Drug for promoting blood circulation for removing blood stasis could treat cerebral infarction by influencing the stem cell paracrine action, inhibiting the nerve cell apoptosis of ischemic area, and promoting restoration of nerve cells and angiogenesis of the half dark area.

关 键 词：活血化瘀 干细胞旁分泌效应 脑梗死 研究 

分 类 号：R285.5[医药卫生—中药学]