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血管活性肠肽对帕金森病大鼠黑质胶质细胞活化及相关炎性因子释放的影响
Effects of vasoactive intestinal peptide on the activation of glia and the expression of associated inflammatory factors in the substantia nigra of Parkinson’s disease rat models
目的 探讨血管活性肠肽(VIP)对帕金森病(PD)大鼠模型中脑黑质胶质细胞活化及相关炎性因子表达的影响。方法 将6-羟多巴胺（6-OHDA）定向注入大鼠右侧纹状体制备PD模型。32只制备成功的PD大鼠随机分为VIP组和模型组，VIP组大鼠腹腔注射VIP 1ml( 20μg/L)，另10只正常大鼠为对照组。分别采用免疫组织化学、Western blotting、RT-PCR方法观察大鼠中脑黑质多巴胺(DA)能神经元、小胶质细胞、星形胶质细胞的数量和形态变化以及肿瘤坏死因子α(TNF-α)和环氧化酶2(COX-2)的表达变化。 结果 模型组大鼠黑质损毁侧小胶质细胞即白细胞分化抗原11b（CD11b）阳性细胞，数量较对照组明显增加(P<0.05)并呈阿米巴样改变，星形胶质细胞(GFAP阳性细胞)数量明显增加(P<0.05)，炎性因子表达水平也明显上升(P<0.05)，DA能神经元数量较对照组明显下降(P<0.05)；与模型组相比，VIP组大鼠损毁侧黑质小胶质细胞和星形胶质细胞数量明显下降(P<0.05)，炎性因子表达水平显著降低(P<0.05)，DA能神经元数量较模型组增加(P<0.05)。 结论 VIP对帕金森病大鼠黑质小胶质细胞和星形胶质细胞的活化具有抑制作用，并可减少相关炎症因子的表达，从而保护黑质DA能神经元。
Objective To investigate the effects of vasoactive intestinal peptide (VIP) on the activation of glia and the expression of associated inflammatory factors in the substantia nigra of the rat model of Parkinson’s disease (PD) induced by 6-hydroxydopamine (6-OHDA). Methods 6-OHDA solution was microinjected into one side of striatum to establish the PD rat model. A total of 32 PD rats were randomly divided into two groups: the VIP group with intraperitoneal injection of the VIP solution 1 ml (20μg/L) and model group with intraperitoneal injection of the normal saline, 16 rats per group. Ten adult normal rats were injected with saline as the control group. The number changes of dopaminergic neurons, microglia that is cluster of diffenentiation 11b (CD11b)-positive cells, astrocytes (GFAP-positive cells) and the expression changes of inflammatory factor (tumor necrosis factor α, cyclooxygenase-2) in substantia nigra of the rats in each group were examined by immunohistochemistry, RT-PCR and Western blotting, respectively. Results Compared to the control group, the numbers of DA neurons, microglia (amoeba-like shaped) and astrocytes in the model group and the VIP group were widely increased (P<0.05), and the expression level of the associated inflammatory factors in the two groups were also increased. In VIP group, the numbers of DA neurons, microglia, astrocytes and the expression level of associated inflammatory factors were decreased compared with the model group (P<0.05). Conclusion VIP has inhibition effects on the activation of microglia and astrocytes, and reduces the expression of related inflammatory factors in the 6-OHDA-induced PD rats. Thus, VIP may protect the DA neurons.
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山东省高等学校科技计划项目;2014年国家级大学生创新创业训练计划项目;潍坊医学院大学生科技创新基金项目
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