Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson’s Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress  

作　　者：LI Yan-rong FAN Hui-jie SUN Rui-rui JIA Lu YANG Li-yang ZHANG Hai-fei JIN Xiao-ming XIAO Bao-guo MA Cun-gen CHAI Zhi 

机构地区：[1]The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine,Shanxi University of Chinese Medicine,Jinzhong,Shanxi Province,030619,China [2]Institute of Brain Science Department,Neurology of First Affiliated Hospital,Shanxi Datong University,Datong,Shanxi Province,037009,China [3]Department of Anatomy and Cell Biology,Department of Neurological Surgery,Spinal Cord and Brain Injury Research Group,Stark Neurosciences Research Institute,Indiana University School of Medicine,Indianapolis,IN,46202,USA [4]Institute of Neurology,Huashan Hospital,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai,200025,China

出　　处：《Chinese Journal of Integrative Medicine》2023年第1期19-27,共9页中国结合医学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(Nos.81703978 and 81102552);the Special Fund for Science and Technology Innovation Team of Shanxi University of Chinese Medicine(No.2022TD1013);the Natural Science Foundation of Shanxi Province(No.201901D111334);the Returned Chinese Scholars Technology Activities Preferred Project,Shanxi Province of China(No.20200026);the Research Project supported by Shanxi Scholarship Council of China(No.2021-142);Shanxi University Science and Technology Innovation Project(No.2019L0724);the Key Science and technology R&D project of Jinzhong(No.Y213004);the Young Scientist Cultivation Program Project,Shanxi University of Chinese Medicine(No.2021PY-QN-03)。

摘　　要：Objective:To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill(WYP) on Parkinson’s disease(PD) model mice.Methods:Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal,PD,and PD+WYP groups,12 mice in each group.One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) was used to establish the classical PD model in mice.Meanwhile,mice in the PD+WYP group were administrated with 16 g/kg WYP,twice daily by gavage.After 14 days of administration,gait test,open field test and pole test were measured to evaluate the movement function.Tyrosine hydroxylase(TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein(GRP78) in striatum and cortex were observed by immunohistochemistry.The levels of TH,GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,ATF6,CHOP,ASK1,p-JNK,Caspase-12,-9 and-3 in brain were detected by Western blot.Results:Compared with the PD group,WYP treatment ameliorated gait balance ability in PD mice(P<0.05).Similarly,WYP increased the total distance and average speed(P<0.05or P<0.01),reduced rest time and pole time(P<0.05).Moreover,WYP significantly increased TH positive cells(P<0.01).Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex.Meanwhile,WYP treatment significantly decreased the protein expressions of GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,CHOP,Caspase-12 and Caspase-9(P<0.05or P<0.01).Conclusions:WYP ameliorated motor symptoms and pathological lesion of PD mice,which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

关 键 词：Wuzi Yanzong Pill Parkinson’s disease dopaminergic neurons endoplasmic reticulum stress apoptosis 

分 类 号：R285.5[医药卫生—中药学]