6-羟多巴胺通过p38 MAPK信号通路诱发大鼠机械痛敏反应  

6-hydroxydopamine induces mechanical hyperalgesia reaction in rats through p38 MAPK signaling pathway

作　　者：马宁宁 罗娜 母童 孙志宏[1,2] MA Ningning;LUO Na;MU Tong;SUN Zhihong(College of Life Sciences,Yan’an University,Yan’an 716000,China;Shaanxi Provincial Research Center for Bioresource Conservation and Utilization Engineering,Yan’an University,Yan’an 716000,China)

机构地区：[1]延安大学生命科学学院,延安716000 [2]延安大学陕西省区域生物资源保育与利用工程技术研究中心,延安716000

出　　处：《神经解剖学杂志》2024年第1期43-49,共7页Chinese Journal of Neuroanatomy

基　　金：陕西省重点研发计划农业领域一般项目(2019NY-099)。

摘　　要：目的:研究p38 MAPK信号通路参与6-羟多巴胺(6-OHDA)诱导的帕金森病(PD)模型大鼠痛敏反应的调节机制。方法:将40只雄性Sprague Dawley(SD)大鼠随机分为4组:假手术组(Sham)、模型组(6-OHDA)、p38 MAPK抑制剂SB203580处理组(6-OHDA+SB203580)、p38 MAPK激动剂茴香霉素(ANS)处理组(6-OHDA+ANS)。采用脑内右侧纹状体立体定向注射6-OHDA的方法建立大鼠PD模型。6-OHDA+SB203580组与6-OHDA+ANS组大鼠注射6-OHDA构建PD模型后分别注射SB203580与ANS进行处理。von Frey纤维丝测痛仪测定大鼠机械缩足阈值(PWT);酶联免疫吸附测定(ELISA)法检测大鼠背根神经节(DRG)中IL-6、IL-1β、TNF-α的含量;real time RT-PCR检测大鼠DRG中IL-6、IL-1β、TNF-α及p38 MAPK的mRNA水平。结果:在6-OHDA诱导的PD模型大鼠DRG中,IL-6、IL-1β、TNF-α和p38 MAPK的表达水平显著升高(P<0.05),大鼠PWT显著下降(P<0.05);而应用激动剂ANS会更进一步地导致大鼠DRG中IL-6、IL-1β、TNF-α和p38 MAPK的表达水平升高,并使大鼠PWT降低;应用抑制剂SB203580后大鼠DRG中IL-6、IL-1β、TNF-α和p38 MAPK的表达水平均显著降低(P<0.05),大鼠PWT显著升高(P<0.05)。结论:6-OHDA可诱导大鼠产生机械性痛敏反应,其分子机制与p38 MAPK信号通路激活有关。Objective:To study the regulatory mechanism of p38 MAPK signaling pathway participate in hyperalgesia reaction in Parkinson’s disease(PD)rats model induced by 6-hydroxy dopamine(6-OHDA).Methods:Forty male Sprague Dawley(SD)rats were randomly divided into four groups:Sham group(Sham),model group(6-OHDA),p38 MAPK inhibitor SB203580 treatment group(6-OHDA+SB203580)and p38 MAPK activator anisomycin(ANS)treatment group(6-OHDA+ANS).PD model was established by intra-striatal injection of 6-OHDA stereotactically.6-OHDA+SB203580 and 6-OHDA+ANS groups was injected with 6-OHDA to establish PD model,and treated with inhibitor SB203580 or activator ANS respectively.The von Frey hairs were applied to measure the mechanical paw withdraw threshold(PWT)of rats.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of IL-6,IL-1β,and TNF-α in rat dorsal root ganglion(DRG).The mRNA levels of genes IL-6,IL-1β,TNF-α,and p38 MAPK in rat DRG was detected by real time RT-PCR.Results:In the DRG of 6-OHDA included PD rats,the expression levels of IL-6,IL-1β,TNF-α,and p38 MAPK were significantly increased(P<0.05),and the PWT of rats were significantly decreased(P<0.05).The application of activator ANS further increased the expression levels of IL-6,IL-1β,TNF-α,and p38 MAPK,and the PWT of rats were decreased.After application of inhibitor SB203580,the expression levels of IL-6,IL-1β,TNF-α and p38 MAPK were significantly decreased in the DRG of rats(P<0.05),and the PWT were significantly increased in rats(P<0.05).Conclusion:6-OHDA induces mechanical hyperalgesia reaction in rats,and the molecular mechanism is related to activation of the p38 MAPK signalling pathway.

关 键 词：帕金森病 p38 MAPK信号通路 神经病理性疼痛 背根神经节 6-羟多巴胺 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]