姜黄素通过肠道微生物改善帕金森病小鼠行为缺陷  

Curcumin improving behavioral deficits in Parkinson’s disease mice via modulation of gut microbiota

作　　者：李文惠 赵志弘 王莉娟 何金晶 刘玉婷 韩秋琴 LI Wen-hui;ZHAO Zhi-hong;WANG Li-juan;HE Jin-jing;LIU Yu-ting;HAN Qiu-qin(Collaborative Innovation Center,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China;School of Pharmacy,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China)

机构地区：[1]上海健康医学院协同科研中心,上海201318 [2]上海健康医学院药学院,上海201318

出　　处：《解剖学报》2025年第2期143-149,共7页Acta Anatomica Sinica

基　　金：上海市“科技创新行动计划”启明星培育扬帆专项(23YF1418200);上海市卫生健康委员会卫生行业临床研究专项青年项目(20234Y0294)。

摘　　要：目的借助粪菌移植研究姜黄素改善帕金森病(PD)小鼠行为缺陷的作用机制。方法腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)建立小鼠亚急性PD模型,收集分离模型组和80 mg/kg姜黄素(Cur)模型治疗组小鼠粪便菌群。通过粪菌移植处理,将小鼠分为粪便菌群溶剂移植组(FMTcon)、模型粪便菌群移植组(FMTmodel)、MPTP模型组(model)以及模型加姜黄素粪便菌群移植组(model+FMTCur)4组。通过转棒、爬杆和旷场实验评估小鼠运动能力,通过免疫荧光观察动物脑黑质部位酪氨酸羟化酶(TH)阳性神经元表达,并检测小鼠中脑部位肿瘤坏死因子α(TNF-α)基因表达,核因子κB(NF-κB)和核苷酸结合寡聚结构域样受体蛋白3(NLRP3)通路相关蛋白表达。结果成功建立小鼠亚急性PD动物模型,收集分离粪便菌群。Model组表现为明显运动障碍,表现转棒维持时间缩短(P<0.05),爬杆时间延长(P<0.05),旷场内总运动距离(P<0.001)和中心区运动时间(P<0.01)明显缩短;黑质部位TH阳性神经元相对表达量显著降低(P<0.01);中脑内TNF-αmRNA表达显著升高(P<0.01),NF-κB(P<0.001)、磷酸化NF-κB(p-NF-κB)(P<0.01)、NLRP3(P<0.001)、Caspase-1(P<0.01)蛋白表达均明显升高。模型粪便菌群移植组(FMTmodel)也出现运动障碍,表现为转棒时间缩短,爬杆时间延长趋势,旷场内总运动距离明显下降(P<0.01)和中心区运动时间缩短趋势;黑质部位TH阳性神经元相对表达量明显下降(P<0.05);中脑内TNF-αmRNA表达明显升高(P<0.01),NF-κB(P<0.05)和Caspase-1(P<0.01)蛋白表达均明显升高。经姜黄素治疗组粪便菌群移植小鼠(model+FMTCur)运动能力有改善,表现为爬杆时间缩短(P<0.05),转棒维持时间(P<0.01)和中心区域运动时间(P<0.05)明显延长;黑质部位TH阳性神经元相对表达量明显增多(P<0.05);中脑内TNF-αmRNA表达明显降低(P<0.01),NF-κB(P<0.001)、p-NF-κB(P<0.01)、NLRP3(P<0.05)、Caspase-1(P<0.01)蛋白表达均明显降低�Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson’s disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1⁃methyl⁃4⁃phenyl⁃1,2,3,6⁃tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)⁃treated group(80 mg/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP⁃induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)⁃positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor⁃α(TNF⁃α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor⁃κB(NF⁃κB)and nucleotide binding oligomerization domain⁃like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P<0.05),prolonged pole climbing time(P<0.05),significantly reduced total movement distance within the open field(P<0.001),and decreased time spent in the central zone(P<0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P<0.01).Moreover,mRNA expression of TNF⁃αin the midbrain increased significantly(P<0.01),along with significant elevations in protein expression of NF⁃κB(P<0.001),phosphorylated NF⁃κB(p⁃NF⁃κB)(P<0.01),NLRP3(P<0.001),and Caspase⁃1(P<0.01).The transplant

关 键 词：帕金森病 粪菌移植 肠道菌群 姜黄素 神经炎症 免疫印迹法 小鼠 

分 类 号：R742[医药卫生—神经病学与精神病学]