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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 effect of vasoactive intestinal peptide (VIP) on the activation of cerebral nigral glia and the expression of related inflammatory factors in Parkinson’s disease (PD) rats. Methods 6-Hydroxydopamine (6-OHDA) was injected into right striatum of rat to prepare PD model. Thirty-two PD rats were randomly divided into VIP group and model group. The VIP group rats were intraperitoneally injected with VIP 1ml (20μg / L) and the other 10 normal rats as the control group. Immunohistochemistry, Western blotting and RT-PCR methods were used to observe the number and morphological changes of dopaminergic neurons, microglia and astrocytes in substantia nigra of rats, and the effect of tumor necrosis factor-α (TNF) -α) and cyclooxygenase 2 (COX-2) expression changes. Results Compared with the control group, the number of CD11b positive cells in the substantia nigra lesion microglial cells in model group was significantly increased (P <0.05) and changed to amoebic change. The number of astrocytes (GFAP (P <0.05), the expression of inflammatory cytokines also increased significantly (P <0.05), the number of DA neurons decreased significantly compared with the control group (P <0.05). Compared with the model group, the VIP group The number of injured nigral microglia and astrocytes in rats was significantly decreased (P <0.05), the expression of inflammatory cytokines was significantly decreased (P <0.05), the number of DA neurons was increased compared with model group (P < 0.05). Conclusions VIP can inhibit the activation of substantia nigra microglial cells and astrocytes in rats with Parkinson’s disease and can reduce the expression of related inflammatory cytokines and thus protect the substantia nigra DA neurons.