血管活性肠肽对帕金森病大鼠黑质多巴胺能神经元存活及小胶质细胞功能的影响  

Effects of vasoactive intestinal peptide on the survival of dopaminergic neurons and activation of microglia in substantia nigra in rat model of the Parkinson's disease

作　　者：刘宗昱 庄文欣[2] 王晓晓[3] 刘金城[1] 李锋杰[2] 付文玉[3] 

机构地区：[1]潍坊医学院,2011级临床医学专业潍坊261053 [2]潍坊医学院医学研究实验中心,潍坊261053 [3]潍坊医学院组织胚胎学教研室,潍坊261053

出　　处：《神经解剖学杂志》2015年第4期487-492,共6页Chinese Journal of Neuroanatomy

基　　金：山东省高等学校科技计划项目(J13LK51);2014年国家级大学生创新创业训练计划项目(201410438002);潍坊医学院大学生科技创新基金项目(KX2014002)

摘　　要：目的:观察血管活性肠肽(VIP)对帕金森病(PD)大鼠黑质多巴胺(DA)能神经元存活和小胶质细胞活化的影响。方法:采用脑立体定位术将6-羟多巴胺注射至纹状体,制备大鼠PD模型。将PD大鼠随机分为VIP组和模型组,VIP组大鼠腹腔注射VIP 1 ml(20 ng/ml)。另10只正常大鼠为对照组。采用免疫组织化学和RT-PCR方法观测各组大鼠黑质DA能(酪氨酸羟化酶(TH)阳性)神经元数量、小胶质细胞(CD11b阳性)的数量和形态变化以及肿瘤坏死因子(TNF-α)和环氧酶-2(COX-2)的表达及相关分子mRNA水平达变化。结果:PD大鼠损毁侧黑质TH阳性神经元数量较对照组明显减少(P<0.05),小胶质细胞(CD11b阳性细胞)数量显著增加(P<0.05),并呈"阿米巴"样改变,TNF-α和COX-2阳性细胞数量明显增加(P<0.05);VIP组大鼠与模型组相比,黑质TH阳性神经元数量明显增加(P<0.05),CD11b阳性细胞数量明显减少(P<0.05),TNF-α和COX-2的阳性细胞数量显著减少(P<0.05)。RT-PCR检测结果可见,模型组大鼠黑质TH mRNA较对照组显著降低,而VIP组TH mRNA较模型组显著升高(P<0.05),模型组CD11b mRNA、TNF-αmRNA表达明显高于对照组,而VIP组大鼠CD11b mRNA、TNF-αmRNA表达显著低于模型组。结论:VIP对6-OHDA所致PD大鼠DA能神经元具有保护作用,并且可以抑制黑质内小胶质细胞活化及相关炎性因子的表达。Objective： To observe the effects of vasoactive intestinal peptide （VIP） on the survival of dopaminergic （DA） neurons and the activation of microglia in substantia nigra of 6-hydroxydopamine （6-OHDA） induced Parkinson＇s disease （PD） rat. Methods ：The PD rat models were established by microinjection of 6-OHDA into one side of striatum. PD rats were randomly divided into two groups, rats VIP group which were injected intraperitoneally with VIP solution （20 ng/ml） and model group rats which were injected with the same volume of saline. Ten normal rats were injected with saline instead of 6-OHDA and were used as the control group. The changes of DA neurons（tyrosine hydroxylase positive, TH-positive）, microglia ceils（CDllb-positive） and the expression of tumor necrosis factor α（TNF-α） and cyclooxygen- ase-2（COX-2） in substantia nigra of rats in three groups were examined using immunohistochemical method. The expres-sion of TH, CDllb and TNF-α at the mRNA level were detected by RT-PCR. Results： The number of TH-positive neu- rons in the substantia nigra pars compacta of PD rats were significantly decreased （ P 〈 0.05 ）, meanwhile the numbers of CDllb-positive ceils with the amoeba-like shape, TNF-ot-positive cells and COX-2-positive cells were significantly in- creased compared with those of the control group （ P 〈 0.05 ）. Compared to the model group, the number of TH-positive neurons in the substantia nigra pars eompacta of VIP group was increased, but CD1 l b-, TNF-α- and COX-2-positive cells of VIP group was decreased significantly （ P 〈 0.05）. The expression trend of TH mRNA, CDllb mRNA, and TNF-α mRNA were consistent with the immunohistoehemical results. Conclusion： VIP has protective effects on the DA neurons in the 6-OHDA induced PD rats, and could inhibit the activation of microglia in substantia nigra and the expression of re- lated inflammatory factors.

关 键 词：血管活性肠肽 帕金森病 小胶质细胞 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]