运动训练对慢性脑灌注不足大鼠髓鞘再生和小胶质细胞表型转变的影响

关键词：血管性认知障碍  运动训练  髓鞘再生  小胶质细胞  表型转变

Keywords:vascular cognitive impairment  physical exercise  remyelination  micorglia  phenotype transformation

摘要：

      摘要 目的：探讨运动训练对慢性脑灌注不足大鼠认知功能及髓鞘再生和小胶质细胞表型转变的影响。 方法：雄性Wistar大鼠随机分为假手术组、对照组和运动训练组，采用双侧颈总动脉结扎法（two-vessel occlusion，2VO）建立大鼠慢性脑灌注不足引起的血管性认知障碍模型。运动训练组于术后48h进行跑笼训练，假手术组和对照组则不予以任何运动干预。各组大鼠于术后第28d采用Morris水迷宫和新物体识别实验评估认知功能，免疫荧光染色观察SMI32和MBP的表达，以及CD86/Iba-1和IGF1/Iba-1双阳性小胶质细胞的数量。 结果：与对照组相比，运动训练组大鼠逃避潜伏期明显缩短，穿越平台的次数和在关键象限停留的时间增加，新物体辨别系数升高（P<0.05）。同时，运动训练组MBP 的表达增强， SMI32的强度降低（P<0.05）。此外，运动训练组IGF1/Iba1阳性的M2 型小胶质细胞数量增加，CD86/Iba1阳性的M1型小胶质细胞激活减少（P<0.05）。 结论：运动训练能够改善慢性脑灌注不足大鼠的认知功能，其机制可能与运动训练诱导小胶质细胞向M2型转变，促进髓鞘再生修复有关。

Abstract:

      Abstract Objective: To explore the effect of physical exercise on cognitive function, remyelination and microglia phenotype transformation in rats with chronic cerebral hypoperfusion. Method: Wistar rats were used to establish vascular cognitive impairment (VCI) models by two-vessel occlusion (2VO) and randomly divided into sham-operated group, control group, and physical exercise group. Rats in the physical exercise group were placed into a programmable, motorized wheel apparatus and began to perform running exercise at 48h after 2VO. The sham group and control group were housed in a standard cage without any targeted training. Rats in each group were assessed for cognitive function using the novel object recognition test and Morris water maze test at 28 days after surgery. The myelin damage and regeneration were observed by SMI32/MBP immunofluorescence staining. The microglia phenotype transformation was detected using CD86/Iba-1 and IGF1/Iba-1 immunofluorescence double-label staining. Result: Morris water maze test showed that physical exercise group spent significantly less time to find the hidden platform and reversed memory deficit, as shown by the greater numbers of platform crossings and longer time spent in the target quadrant. Novel object recognition test showed that physical exercise can also significantly improve the capacity to recognize novel objects in rats with chronic cerebral hypoperfusion. At the same time, the SMI32/MBP immunofluorescence staining showed that physical exercise significantly reduced myelin damage, as shown by the enhanced MBP immunostaining and the decreased fluorescence intensity of SMI32 and its fluorescence intensity ratio to MBP. Furthermore, IGF1/Iba1 and CD86/Iba1 immunofluorescence double staining revealed that physical exercise upregulated the number of IGF1/Iba1 positive M2 microglia and decreased the number of CD86/Iba1 positive M1 microglia. Conclusion: Physical exercise can improve the cognitive function of rats with chronic cerebral hypoperfusion possibly by modulating the microglia phenotype transformation from M1 to M2, and then promoting remyelination.