香椿子多酚通过抑制P38MAPK信号通路减轻帕金森病大鼠的神经炎症反应  

Polyphenols from Toona sinensis seeds alleviate neuroinflammation in rats with Parkinson's disease via inhibiting p38MAPK signaling pathway

作　　者：庄文欣 陈超 马一闻 宋乐乐 吕娥[3] 付文玉[3] ZHUANG Wenxin;CHEN Chao;MA Yiwen;SONG Lele;LYU E;FU Wenyu(Medical Research Center,Weifang Medical University,Weifang 261053,China;College of Biological Sciences and Technology,Weifang Medical University,Weifang 261053,China;Department of Histology and Embryology,Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院医学研究实验中心,山东潍坊261053 [2]潍坊医学院生物科学与技术学院,山东潍坊261053 [3]潍坊医学院组织学与胚胎学教研室,山东潍坊261053

出　　处：《细胞与分子免疫学杂志》2019年第9期794-799,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家重点基础研究发展计划子课题(2012CBA01304);山东省自然科学基金(ZR2014HL043);山东省中医药科技发展计划项目(2015-234,2017-214):国家级大学生创新创业计划|(201910438017);潍坊医学院博士启动基金(2017BSQD26);潍坊医学院大学生科技创新基金(KX2018017)。

摘　　要：目的探讨香椿子多酚(PTSS)对帕金森病(PD)大鼠神经炎症的抑制作用及机制。方法成年雄性SD大鼠单侧纹状体内注射6-疑多巴胺(6-OHDA)造模。造模成功大鼠随机分为模型组、PTSS处理组,另设一组正常大鼠为对照组,每组10只。30 d后,采用阿朴吗啡(APO)腹腔注射诱导大鼠的旋转行为,检测各组大鼠的行为改变。免疫组织化学染色法观测各组大鼠黑质酪氨酸務化酶(TH)阳性的多巴胺(DA)能神经元、钙离子结合接头蛋白分子l(Ibal)阳性的小胶质细胞、胶质原纤维酸性蛋白(GFAP)阳性的星形胶质细胞形态和数量变化;免疫组织化学染色法检测黑质诱导型一氧化氮合酶(iNOS)、核因子KBp65(NF-KBp65)、P38丝裂原活化蛋白激酶(p38MAPK)和磷酸化的p38MAPK(p-p38MAPK)的表达;Western blot法检测大鼠黑质TH、GFAP、p38MAPK、p-p38MAPK蛋白水平。结果PTSS处理组大鼠的旋转圈数较模型组明显减少。模型组大鼠损毁侧黑质TH阳性细胞较对照组显著减少,PTSS处理后,TH阳性细胞数量以及蛋白表达明显增加。与对照组相比,模型组大鼠损毁侧黑质Ibal、GFAP、iNOS、NF-kB、p38MAPK和p-p38MAPK蛋白含量显著增加。PTSS处理后,上述蛋白的表达均明显减弱,蛋白含量显著降低。结论PTSS通过抑制p38MAPK信号通路,减少炎症因子的表达,对PD大鼠DA能神经元起保护作用。Objective To explore the inhibitory effects of polyphenols from Toona sinensis seeds(PTSS)on neuroinflammation and the underlyi ng mechanism in rats with Parkins on's disease(PD).Methods PD rat models were prepared by stereotaxic injection of 6-hydroxydopamine(6-OHDA)into one side of striatum of Sprague-Dawley male rats.Model rats were randomly divided into model group and PTSS group(n=10),and a normal control group was set as well(n=10).The rotational behavior of rats was induced by intraperitoneal injection of apomorphine(APO)after 30 days,and the behavioral cha nges of rats from each group were investigated.The morphological and quantity changes of DA n euro ns(tyrosine hydroxylase positive,TH-positive),microglia cells(ionized calcium binding adaptor molecule-1,Ibal-positive)and astrocytes(glial fibrillary acidic protein,GFAP-positive)in substantia nigra(SN)of rats from each group were examined by immunohistochemistry.Inducible nitric oxide synthase(iNOS),nuclear factor-KB p65(NF-KBp65),p38 mitogereactivated protein kinase(p38MAPK)and phosphor-p38 mitogen-activated protein kinase(p-p38MAPK)levels were evaluated through immunohistochemical staining.The protein levels of TH,GFAP,p38MAPK and p-p38MAPK in SN were examined by Western blot analysis.Results The number of rotations in the rats of the PTSS group was significantly reduced compared with that in the model group.The number of TH-positive cells in the model group was much less than that in the control group.The number and protein levels of TH-positive cells were enhanced significantly by PTSS intervention.Compared with the control group,the protein levels of Ibal,GFAP,iNOS,NF-kB,p38MAPK and p-p38MAPK in the injured side of the model group significantly increased,which could be suppressed significantly by PTSS intervention.Conclusion PTSS dem on strates protective effects on DA n euro ns by inhibit!ng p38MAPK sign aling pathway and reduci ng the expressi on of inflammatory factors in PD rats.

关 键 词：香椿子多酚(PTSS) 神经炎症 帕金森病 大鼠 黑质 P38MAPK通路 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]