目的:研究运动训练对脑梗死大鼠侧脑室室管膜下区(SVZ)内源性神经干细胞迁移的影响,并观察基质细胞衍生因子-α(SDF1-α)/趋化因子(CXCR4)信号通路在其中的作用.方法:成年Wistar大鼠81只,采用线栓法制作大脑中动脉阻塞再灌注模型,随机分为运动训练组(E,n=18)、运动训练+AMD3100组(EA,n=18)、对照组(C,n=18)、对照+AMD31 00组(CA,n=18)和假手术组(S,n=9).E和EA组从术后第3天起每天予以跑笼运动训练;EA和CA组于术后第2天起隔天注射AMD3100;C、CA和S组则置于普通笼内饲养,不予以任何针对性措施.所有大鼠在造模术后第7、14、21d进行神经功能评分(mNSS),并采用免疫荧光法观察大鼠梗死侧SVZ、纹状体、梗死周围皮质BrdU和Dcx双阳性细胞数,以及梗死边缘区SDF-1α及其受体CX-CR4的表达情况.结果:在造模术后第14天和第21天,E组的mNSS评分均明显优于其他各组(P<0.05).免疫荧光结果显示:术后第7、14、21天,E组BrdU和Dcx双阳性细胞及SDF-1α、CXCR4阳性细胞在相应区域的表达均多于C组(P<0.05)、CA组(P<0.001)和S组(P<0.001).此外,术后第14天和第21天,E组的BrdU和Dcx双阳性细胞数在各个区域的表达也明显多于EA组(P<0.05),E和EA组的SDF-1α、CXCR4阳性细胞在梗死边缘区的表达差异无显著性意义(P>0.05).结论:运动训练促进脑梗死大鼠神经功能的恢复,其机制可能与运动训练上调SDF-1 α/CXCR4的表达,进而促进SVZ的内源性神经干细胞迁移有关.
Objective: To examine whether physical exercise can improve functional recovery by enhancing neural stem cells (NSCs) migration from subventricular zone (SVZ) through stromal-derived factor- 1 a ( SDF- 1 ct )/chemokine re- ceptor-4(CXCR4) pathways in rats after ischemic stroke. Method: Eighty-one adult Wistar rats after transient middle cerebral artery occlusion(tMCAO) were randomly divided into five groups: physical exercise group (E, n=18), physical exercise combined with AMD3100 injec- tion group (EA, n=18), Both of these two groups were given running exercise daily at 3 days after MCAO. Control group (C, n=18), control combined with AMD3100 injection group (CA, n=18) and sham-operated group (S, n=9), which all were fed in standard cages without any special training exercise. The rats were sacri- ficed on the 7th, 14th, 21st day after evaluating ~the neurological function with modified neurological severity score(mNSS). Bromodeoxyaridine(BrdU) and doublecirtin(Dcx) double-positive cells were observed in the ipsi- lateral SVZ, striatum and peri-infarct cortex. SDF-lct and CXCR4 were checked in the peri-infarct region. Result: The mNSS score in E group was much better than that in other groups (P〈0.05) at the 14th days and 21st days after MCAO (P〈0.05). Immunofluorescence analysis showed amount of BrdU and Dcx double posi- tive ceils and SDF-lct, CXCR4 positive cells displayed a significantly higher expressions in E group than that in C group (P〈0.05), CA group(P〈0.001) and S group (P〈0.001) at each time points and that in EA group at the 14th and 21st days (P〈0.05) after MCAO in the corresponding regions. In addition, physical exercise signif- icantly increased the amount of SDF-lct and CXCR4-positive cells but no significant difference(P〉0.05). Condusion: Physical exercise can enhances neurological function possibly by mediating endogenous NSCs mi- gration from SVZ to the peri-infarct region via SDF-la/CXCR4