GJ-4对帕金森病模型小鼠的保护作用及其机制  

Protective Effect and Mechanism of GJ-4 on Mice of Parkinson's Disease

作　　者：袁方玉 盛婵娟 鞠程 李方园 臧彩霞 尚俊美 刘慧 鲍秀琦 张丹 YUAN Fangyu;SHENG Chanjuan;JU Cheng;LI Fangyuan;ZANG Caixia;SHANG Junmei;LIU Hui;BAO Xiuqi;ZHANG Dan(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《医药导报》2022年第11期1582-1588,共7页Herald of Medicine

基　　金：国家自然科学基金资助项目(81630097,81773718);中国医学科学院医学与健康科技创新工程资助项目(2016-I2M-3-011);国家“重大新药创制”科技重大专项资助项目(2018ZX09711001-003-020,2018ZX09711001-003-005,2018ZX09711001-008-005);中国医学科学院中央高校基本科研业务费(2018RC35002)。

摘　　要：目的观察中药栀子提取物GJ-4对亚急性帕金森病(PD)模型小鼠的保护作用,并探索其可能作用机制。方法将C57/BL6J雄性小鼠随机分成空白对照组、模型对照组、GJ-4各剂量组(25,50,100 mg·kg^(-1))和阳性对照组(左旋多巴组)。除空白对照组外,其他小鼠以1-甲基-4-苯基-1,2,3,6-四氢吡啶建立PD模型。GJ-4各剂量组与阳性对照组小鼠分别灌胃不同剂量GJ-4和左旋多巴,空白对照组与模型对照组灌胃相同剂量0.5%羧甲基纤维素钠,均每天1次,连续12 d。免疫组化检测小鼠黑质酪氨酸羟化酶(TH)阳性神经元数目,蛋白印迹法(Western blot)测定小鼠中脑TH、iNOS蛋白含量变化,实时荧光定量PCR(qPCR)检测小鼠中脑肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及凋亡相关蛋白Bax、Bcl-2mRNA表达。结果与模型对照组比较,GJ-450 mg·kg^(-1)组和GJ-4100 mg·kg^(-1)组小鼠运动障碍改善,且呈剂量依赖性(P<0.05);与模型对照组比较,GJ-4100 mg·kg^(-1)组小鼠黑质TH阳性神经元数目显著升高(P<0.01),中脑TH蛋白表达明显升高(P<0.01),中脑TNF-α、IL-1β表达降低(P<0.05),中脑Bax降低(P<0.05),中脑Bcl-2表达升高(P<0.05)。结论GJ-4对PD模型小鼠具有保护作用,其机制可能是抑制小鼠中枢神经系统炎症因子产生和细胞凋亡。Objective To investigate the neuroprotective effect of GJ-4(extracted from traditional Chinese medicine Gardenia jasminoides J.Ellis)in MPTP-induced sub-acute Parkinson's disease(PD)mice model,and to explore the underlying mechanisms.Methods Male C57/BL6J mice were randomly divided into control group,MPTP model group,GJ-4-treated groups(25,50 and 100 mg·kg^(-1))and L-Dopa treated group.The subacute PD model was developed by intraperitoneal injection of MPTP.Mice in all three GJ-4 treated groups and the L-Dopa group were orally administrated corresponding substances while mice in control group and MPTP model group was given 0.5%CMC-Na at same dose.All substances were given once a day for consecutive 12 days.Immunohistochemistry was used to detect tyrosine hydroxylase(TH)positive neuron in substantial nigra.Western blot was employed to examine TH and iNOS protein expression in midbrain;The mRNA expression level of inflammatory cytokine TNF-αand IL-1β,apoptosis-related protein Bax and Bcl-2 in the midbrains of mice were examined by qPCR.Results Comparing with MPTP-challenged mice,the motor behaviors of mice administrated with GJ-450 mg·kg^(-1)and 100 mg·kg^(-1)significantly improved in a dose-related manner(P<0.05).Comparing with MPTP-challenged mice,GJ-4100 mg·kg^(-1)could significantly increase the number of TH positive neuron in substantial nigra(P<0.01),TH protein expression in the midbrains of mice(P<0.01).And GJ-4 inhibit the mRNA expression of inflammatory cytokine TNF-αand IL-1βin mice midbrain(P<0.05),inhibited Bax mRNA expression(P<0.05)in mice midbrain,and elevated Bcl-2 mRNA expression(P<0.05)in mice midbrain.Conclusion GJ-4 exerts a neuroprotective effect on sub-acute PD mice.And the underlying mechanisms may be through inhibiting neuroinflammation and neuronal apoptosis in mice central nervous system.

关 键 词：GJ-4 栀子提取物 帕金森病 神经炎症 凋亡 

分 类 号：R286[医药卫生—中药学] R95[医药卫生—中医学]