中国实验动物学报2026，Vol.34Issue(7)：949-959,11.DOI:10.3969/j.issn.1005-4847.2026.07.002
鱼藤酮对大鼠肠-脑轴神经层面α-突触核蛋白聚集的影响
Effect of rotenone on α-synuclein aggregation in the gut-brain axis of rats at the neural level
摘要
Abstract
Objective To investigate the pathological injury and abnormal deposition of α-synuclein(α-syn)in the striatum,substantia nigra,dorsal motor nucleus of the vagus nerve,spinal cord,and colon at different time points in a rotenone-induced rat model of Parkinson's disease(PD).Methods Thirty-six specific pathogen-free male SD rats were randomly divided into control and rotenone groups(n=18).The rotenone group was administered rotenone at 30 mg/(kg·d)by gavage to establish the PD rat model,while the control group received an equal volume of 0.5%sodium carboxymethylcellulose vehicle.Both groups were further subdivided into 3-,6-,and 9-week subgroups(n=6)according to gavage duration.After continuous intervention,the colon,thoracic spinal cord,dorsal motor nucleus of the vagus nerve,substantia nigra,and striatum were harvested.Behavioral changes were evaluated using open-field,balance beam,and rotarod tests.Hematoxylin and eosin(HE)staining was used to observe pathological injury in the colon,intermediolateral nucleus of the spinal cord,dorsal motor nucleus of the vagus nerve,substantia nigra,and striatum.Nissl staining was performed to assess neuronal damage by examining the morphology,distribution,and quantity of Nissl bodies.Immunohistochemistry was applied to detect α-syn expression levels in the four tissue layers,while immunofluorescence was used to measure tyrosine hydroxylase(TH)expression(a key enzyme for dopamine synthesis)in the substantia nigra,as well as TH and α-syn in the striatum.Results With prolonged gavage duration,rotenone-treated rats exhibited decreased total distance and average velocity in the open-field test,prolonged latency to cross the balance beam,and reduced time on the rod,moving distance,and falling speed in the rotarod test compared with controls(P＜0.05).HE and Nissl staining revealed that pathological injury was aggravated in a gavage time-dependent manner,characterized by Nissl body dissolution,abnormal shrinkage,and gradual reduction in the number of neuronal cell bodies.The rotenone group showed significantly elevated α-syn expression compared with the control group(P＜0.05),accompanied by decreased TH expression in the substantia nigra and striatum(P＜0.05).Conclusions In this rotenone-induced rat model of PD,pathological injury and abnormal α-syn deposition in the colon,spinal cord,dorsal motor nucleus of the vagus nerve,substantia nigra,and striatum were aggravated in a time-dependent manner;this led to progressive downregulation of TH expression in the substantia nigra,with the most significant changes observed at 9 weeks.This model systematically recapitulates the key progressive process of PD pathology spreading along the gut-brain axis to ultimately cause core functional deficits,providing a reliable animal model for the staged and multi-layered investigation of the disease pathogenesis.However,the specific propagation pathway of α-syn along the gut-brain axis was not elucidated,and the relevant findings require further validation in subsequent research.关键词
帕金森病/鱼藤酮/肠-脑轴/α-syn/动物模型Key words
Parkinson's disease/rotenone/gut-brain axis/α-synuclein/animal model分类
生物科学引用本文复制引用
位娜鑫,谌盈帆,齐小荣,耿小涵,张倩,张煜梽,李敏..鱼藤酮对大鼠肠-脑轴神经层面α-突触核蛋白聚集的影响[J].中国实验动物学报,2026,34(7):949-959,11.基金项目
国家自然科学基金(82274613). Funded by National Natural Science Foundation of China(82274613). （82274613）
