天麻钩藤饮通过抑制坏死性凋亡通路改善帕金森病小鼠的运动功能障碍

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Tianma Gouteng Granule improves motor deficits in mouse models of Parkinson's disease by regulating the necroptosis pathway

CHENDandnnian，nglno，ingn，ng，G，O2 SchoolofportsedicineHubeironcialKeybotoryeciseninndtoingWuanortssitWua 430079，inofleiee;l EducationndHealth，uangxiedicaliversity，nningo1in

Abstract：ObjectiveToinvestigatetheefectsofformulatedgranulesof TianmaGoutengYin（TGY）onmotordeficitsina mousemodelof1-methyl-4-phenyl-1，2，36-tetrahydropyridine （MPTP）-inducedsubacuteParkinson's disease（PD）andexplore the possible molecular mechanisms.Methods Ninety C57BL/6 mice were randomized equall into6groups，including a control group， a PD model group， a NEC-1 （ 6.5mg/kg treatment group， two TGY treatment groupsat5 and 2.5g/kg， and a Madopar （76mg/kg） treatment （positivecontrol） group.Mousemodelsof PDwere established byintraperitoneal injectionof MPTP （30mg/kg） for5consecutive days with thecorresponding treatments for 15days.The mice wererandomly selected for motor function tests.Western blotting was used to detect the changes in expressions of TH， α -syn，RIPK1，K3din thestriatumofthemice.Network pharmacologyanalysisandmoleculardockingstudieswereperformed toexploreTGYmediatedregulationof thenecroptosispathwayforPDtreatmentResults Comparedwiththoseinthecontrolgroup，thePD model mice exhibited obviousmotordeficitswith significantly increased α -synproteinexpressionandloweredTH protein expressioninthestriatum.TreatmentwithNEC-1obviouslyimprovedmotordeficits，inhbitedthenecroptosispathwayand alleviated thechangesin TH and α -syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested thatthetherapeuticeffectof TGYinPDwasassciatedwith the modulationofRIPK1，akeyproteininthe necroptosis pathway.InPDmousemodels，TGYtreatmentatthetwodosessignificantlyimprovedmotordeficitsof themice， increasedTHexpression，anddecreasedtheexpressionsof α -synand necroptosis-related proteinsinthestriatum.Conclusion TGY can effectively inhibit the necroptosis pathway， increase TH expression and decrease α -syn expression in the striatum to improve motor deficits in PD mice.

Keywords：Parkinson'sdisease;Tianma Gouteng Yin;motordeficits;necroptosispathway

帕金森病（PD）是中老年人多发的以静止性震颤等运动症状为主要临床表现的第二大神经退行性疾病。（剩余18791字）