目的 探讨丰富环境(EE)对血管性痴呆大鼠侧脑室室管膜下区(SVZ)神经再生的影响。方法 29只大鼠分成假手术组(n=5)、血管性痴呆组(VD组,n=12)和丰富环境组(EE组,n=12)。采用两血管阻断法(2-VO)制作血管性痴呆模型。VD组和假手术组常规饲养条件下饲养,EE组给予丰富环境干预。30 d后免疫组织化学染色观察SVZ微管相关蛋白Doublecortin (DCX)与外源性细胞增殖标记物BrdU的表达,免疫荧光双标观察SVZ DCX/Ki67、DCX/p-cAMP反应元件结合蛋白(CREB)的共表达情况。结果 与假手术组相比,VD组BrdU+细胞数目(t=2.989, P=0.026)、DCX+细胞平均光密度值(t=3.069, P=0.005)增加;与VD组比较,EE组BrdU+细胞数目(t=3.067, P=0.027)、DCX+细胞平均光密度值(t=2.907, P=0.011)进一步增加。EE组DCX/Ki67 (t=2.994, P=0.040)、DCX/p-CREB(t=4.707, P=0.009)共表达细胞高于VD组。结论 丰富环境可通过CREB信号通路上调血管性痴呆大鼠SVZ神经再生水平。
Objective To explore the effect of enriched environment on neuroregeneration in subventricle zone (SVZ) of rats with vascular dementia. Methods All rats were divided into sham group (n=5), vascular dementia group (VD group, n=12) and enriched environment group (EE group, n=12). Then, 2-VO method was applied to make the vascular dementia model. The sham group and VD group received conventional breeding environment for 30 days, while EE group was subjected to enriched environment for 30 days. Immunohistochemistry was applied to detect the BrdU and Doublecortin (DCX) expression in SVZ, and DCX/Ki67, DCX/p-cAMP-response element binding protein (CREB) expression in SVZ was assessed by immunofluorescence double-labeling technique. Results Compared with the sham group, the number of DCX+ cells (t=2.989, P=0.026) and BrdU+ cells (t=3.069, P=0.005) increased in VD group, and increased more in EE group (t=3.067, P=0.027; t=2.907, P=0.011). Besides, the number of the DCX/Ki67 (t=2.994, P=0.040) and DCX/p-CREB (t=4.707, P=0.009) cells was significantly higher in EE group than in VD group. Conclusion Enriched environment could up-regulate the neuroregeneration capacity in SVZ of rats with vascular dementia through CREB signal pathway.
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