南方医科大学学报2024，Vol.44Issue(5)：876-884,9.DOI:10.12122/j.issn.1673-4254.2024.05.09
Bmal1可能介导了丁酸钠对帕金森病小鼠的神经保护作用
Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease
摘要
Abstract
Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.关键词
丁酸钠/帕金森病/肠-脑轴/Bmal1Key words
sodium butyrate/Parkinson's disease/gut-brain axis/Bmal1引用本文复制引用
王飞霞,张政,孙艳,杨柳菁,郭桐彤,潘夜厅,丁嵩涛,蒋林,刘含登..Bmal1可能介导了丁酸钠对帕金森病小鼠的神经保护作用[J].南方医科大学学报,2024,44(5):876-884,9.基金项目
重庆市自然科学基金(cstc2017jcyjAX0113) （cstc2017jcyjAX0113）
重庆市青年创新人才培养计划项目(CY220404) （CY220404）
重庆医科大学大学生导师制创新人才培养项目(LTMCMTS202202) （LTMCMTS202202）
