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

doi:10.16098/j.issn.0529-1356.2016.02.005

解剖学报 ›› 2016, Vol. ›› Issue (2): 178-184.doi: 10.16098/j.issn.0529-1356.2016.02.005

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

庄文欣¹ 刘宗昱^2王雪净³李晓健⁴刘金城^5付文玉^6*

1. 潍坊医学院医学研究实验中心; 2. 2011级临床医学专业; 3. 科研处; 4. 2013级生物技术专业;5. 2012级生物技术专业; 6. 组织学与胚胎学教研室，山东潍坊 261053

收稿日期:2015-07-10 修回日期:2015-08-10 出版日期:2016-04-06 发布日期:2016-04-06
通讯作者: 付文玉 E-mail:fuwenyu.2007@163.com
基金资助:
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

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

ZHUANG Wen-xin¹ LIU Zong-yu² WANG Xue-jing³LI Xiao-jian⁴ LIU Jin-cheng⁵ FU Wen-yu ^6*

1. Medical Research Center; 2. Grade 2011 of Clinical Medicine; 3. Department of Research Administration;4. Grade 2013 of Biotechnology Speciality; 5. Grade 2012 of Biotechnology Speciality; 6. Department of Histology and Embryology, Weifang Medical University, Shangdong Weifang 261053, China

Received:2015-07-10 Revised:2015-08-10 Online:2016-04-06 Published:2016-04-06
Contact: FU Wen-yu E-mail:fuwenyu.2007@163.com

摘要/Abstract

摘要：

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。

Abstract:

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.

庄文欣刘宗昱王雪净李晓健刘金城付文玉*. 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[J]. 解剖学报, 2016, (2): 178-184.

ZHUANG Wen-xin LIU Zong-yu WANG Xue-jing LI Xiao-jian LIU Jin-cheng FU Wen-yu*. 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[J]. AAS, 2016, (2): 178-184.

参考文献

［1］Labandeira-Garcia JL, Rodríguez-Perez AI, Villar-Cheda B, et al. Rho kinase and dopaminergic degeneration a promising therapeutic target for Parkinson’s disease［J］. Neuroscientist, 2015, 21(6): 616-629.
［2］Yan J, Fu Q, Cheng L, et al. Inflammatory response in Parkinson’s disease［J］. Mol Med Rep, 2014, 10(5): 2223-2233.
［3］Deleidi M, Gasser T. The role of inflammation in sporadic and familial Parkinson’s disease［J］. Cell Mol Life Sci, 2013, 70(22): 4259-4273.
［4］Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions［J］. Amino Acids, 2013, 45(1): 25-39.
［5］Waschek JA. VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair［J］. Br J Pharmacol, 2013, 169(3): 512-523.
［6］Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates［M］. Sydney:Academic Press, 1985: 87-92.
［7］Wang XX,Fu WY, Zhuang WX, et al. Improvement of rat model of Parkinson’s disease by unilateral striatal two-point and two-spot injection with 6-hydroxydopamine［J］. Chinese Journal of Neuroanatomy, 2015, 31(2): 187-192. (in Chinese)
王晓晓，付文玉，庄文欣，等. 改良纹状体内两点注射6-OHDA法制备大鼠帕金森病模型［J］. 神经解剖学杂志，2015，31(2): 187-192.
［8］Myhre O, Utkilen H, Duale N, et al. Metal dyshomeostasis and inflammation in Alzheimer’s and Parkinson’s diseases: possible impact of environmental exposures［J］. Oxid Med Cell Longev, 2013, 2013: 726954.
［9］Richardson JR, Hossain MM. Microglial ion channels as potential targets for neuroprotection in Parkinson’s disease［J］. Neural Plast, 2013, 2013: 587418.
［10］Streit WJ, Conde JR, Fendfick SE, et al. Role of microglia in the central nervous system’s immune response［J］. Neurol Res, 2005, 27(7): 685-691.
［11］OuchiY, Yagi S, Yokokura M, et al. Neuroinflammation in the living brain of Parkinson’sdisease［J］. Parkinsonism Relat Disord, 2009, 15(Suppl 3): S200-S204.
［12］Long-Smith CM, Sullivan AM, Nolan YM. The influence of microglia on the pathogenesis of Parkinson’s disease［J］. Prog Neurobiol, 2009, 89(3): 277-287.
［13］Zhuang WX, Fu WY, Lü E, et al. Changes of microglia and astrocyte in substantia nigra of 6-OHDA model rats of Parkinson’sdisease［J］. Acta Anatomica Sinica, 2010, 41(3): 344-348.(in Chinese)
庄文欣，付文玉，吕娥，等. 帕金森病大鼠黑质小胶质细胞及星形胶质细胞的变化［J］. 解剖学报，2010, 41(3): 344-348. 
［14］Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and-2 in neuroinflammation: implications for translational research［J］. Trends Pharmacol Sci, 2009, 30(4): 174-181.
［15］Saijo K, Crotti A, Glass CK. Regulation of microglia activation and deactivation by nuclear receptors［J］. Glia, 2013, 61(1): 104-111.
［16］Peterson LJ, Flood PM. Oxidative stress and microglial cells in Parkinson’s disease［J］. Mediators Inflamm, 2012, 2012: 401264.
［17］Korkmaz OT, Tuncel N, Tuncel M, et al. Vasoactive intestinal peptide (VIP) treatment of Parkinsonian rats increases thalamic gamma-aminobutyric acid (GABA) levels and alters the release of nerve growth factor (NGF) by mast cells［J］. J Mol Neurosci, 2010, 41(2): 278-287.
［18］Bensinger SJ, Tontonoz P. A Nurr1 pathway for neuroprotection［J］. Cell, 2009, 137(1): 26-28.

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

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