盲肠注射α-syn纤维体诱导PD小鼠模型的构建  

Construction of a new PD model induced by injection ofα-syn into the cecum

作　　者：田哲 韩超[2] 莫淑婷 雷新 张茹梦 王晓宇 陈育华 TIAN Zhe;HAN Chao;MO Shuting;LEI Xin;ZHANG Rumeng;WANG Xiaoyu;CHEN Yuhua(不详;Graduate School of Bengbu Medical University,Bengbu Anhui 233030,China)

机构地区：[1]蚌埠医科大学研究生院,233030 [2]中国科学技术大学附属第一医院(安徽省立医院)神经内科,230001 [3]中国科学技术大学附属第一医院(安徽省立医院)康复医学科,230001 [4]中国科学技术大学附属第一医院(安徽省立医院)药学部,230001

出　　处：《中国神经免疫学和神经病学杂志》2025年第2期106-111,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：2022年安徽省重点研究与开发计划项目基金(2022e07020021);安徽省自然科学基金(2008085QH366);中国博士后面上项目一等资助(2021M690147)。

摘　　要：目的构建一种新的帕金森病(Parkinson disease,PD)肠-脑轴研究模型,探讨α-突触核蛋白(α-synuclein,α-syn)肠-脑传播部位及途径,为PD的发病机制研究提供一定的依据。方法选取健康雄性野生型C57小鼠(8周龄)26只,体重20~24 g,随机分为α-syn纤维体(α-syn PFFs)盲肠注射组6只、α-syn PFFs十二指肠注射组6只、磷酸盐缓冲液(phosphate buffered saline,PBS)盲肠注射组6只、PBS十二指肠注射组3只、未干预野生小鼠组5只。体外诱导构建α-syn PFFs,将α-syn PFFs注射至小鼠盲肠(模拟人类阑尾组织)制备PD肠-脑轴模型,同时设置一组十二指肠注射组,2个月后免疫组织化学染色法检测小鼠脑内α-syn的沉积情况;并采用免疫印迹法检测小鼠结肠、小肠和盲肠病理性α-syn沉积情况。结果电镜证实α-syn单体可在体外聚集形成纤维体;α-syn PFFs注射至小鼠盲肠可引起脑内多区域及肠道中α-syn的传播和沉积;相比盲肠注射组,十二指肠注射组在结肠中发生更多病理性α-syn沉积。结论本研究构建了新的α-syn“肠-脑”轴传播的小鼠模型,为更深层次的PD机制研究以及防治新策略提供了新的科学依据。Objective A new gut-brain axis research model of Parkinson s disease(PD)was established to explore the location and pathway of the gut-brain transmission ofα-synuclein(α-syn),and to provide a certain basis for the pathogenesis of PD.Methodsα-syn fibrosomes(α-syn PFFs)was induced fromα-syn monomers in vitro.Twenty-six healthy male wild-type C57 mice(8 weeks of age)with body weight of 20-24 g were randomly divided into these groups:6 mice receivingα-syn PFFs injection in the cecum,6 mice receivingα-syn PFFs injection in the deudenum,6 mice receiving phosphate buffered saline(PBS)injection in the cecum,3 mice receiving PBS in the deudenum and 5 untreated wild type mice.Upon modeling,the mouse cecum(to simulate the human appendix)and duodenum was injected withα-syn PFFs,two months later,the deposition ofα-syn in the brain was detected by immunohistochemical staining.Besides,the deposition ofα-syn in the colon,small intestine and cecum was detected by western blot.Results Electron microscope showed thatα-syn monomer could aggregate to form fibrous body in vitro;injection ofα-syn PFFs into mouse cecum could induceα-syn deposition in the intestine and brain.The intestinal injeciton ofα-syn injected duodenum formed more aggregatedα-syn in the colon than those injected in cecum.Conclusions In this study,a new mouse model ofα-syn"gut-brain"axis transmission was established,which provided a new scientific basis for further research on the mechanism of PD and new strategies for prevention and treatment.

关 键 词：帕金森病 Α-突触核蛋白 肠脑轴 阑尾 动物模型 

分 类 号：R742.5[医药卫生—神经病学与精神病学]