摘要
目的:探讨佛手散对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠的治疗作用,并研究其神经保护作用相关机制。方法:将50只雄性C_(57)BL/6C小鼠随机分为5组,即正常对照组、模型对照组、佛手散100、300 mg/kg组和沙芬酰胺50 mg/kg组,除正常对照组注射等体积生理盐水外,其余各组均每天腹腔注射30 mg/kg的MPTP,连续注射5 d。造模完成后连续给药3 w,于末次给药后1 h,进行行为学检测。并采用高效液相色谱电化学法(HPLC-ECD)检测小鼠纹状体中多巴胺(DA)含量;采用免疫组织化学法检测黑质中酪氨酸羟化酶(TH)免疫阳性细胞情况;采用酶联免疫吸附法(Elisa)检测黑质中前列腺素E2(PGE2)含量;采用Western blot技术测定小鼠纹状体中α-突触核蛋白(α-Syn)和环氧化酶-2(COX-2)蛋白表达情况。结果:与正常对照组相比,模型对照组小鼠在行为学中爬杆和横木行走时间显著延长、自主活动的纵向探索次数明显减少,纹状体中DA含量显著降低,小鼠多巴胺神经元明显损伤,黑质中TH免疫阳性细胞急剧下降,同时纹状体中α-Syn蛋白、COX-2蛋白表达明显上调,黑质中代谢产物PGE2显著增加(P<0.05或P<0.01)。与模型对照组相比,佛手散100、300 mg/kg组能显著减少PD模型小鼠爬杆和横木行走时间、增加纵向探索次数,增加TH免疫阳性细胞,显著下调小鼠纹状体中α-Syn、COX-2蛋白表达,降低黑质中PGE2含量。结论:佛手散对PD的潜在治疗作用可能与其能够减少α-Syn生成,抑制MAO-B活性有关。其详细的分子机制还有待进一步深入研究。
Objective:To explore the therapeutic effect and neuroprotective mechanism of Foshou San on MPTP induced Parkinson’s disease.Methods:50 male C_(57)BL/6 C mice were randomly divided into five groups:Control group,Model group,Foshou San 100 mg/kg group were intraperitoneally injected with saline water,while all other mice were intraperitoneally injected with 30 mg/kg MPTP,once a day for consecutive 5 days.After modeling,the mice were intragastrically administrated with Foushou San for 3 weeks,and the behavioral tests were performed 1 h after the last administration.The level of DA in the striatum was determined by HPLC-ECD,the immune positive cells of TH were observed by immunohistochemistry,the PGE2 level was determined by ELISA,the protein expressions ofα-Syn and COX-2 were determined by Western blotting.Results:Compared with Control group,the time of the pole climbing test and the beam walk test for Model group were significantly increased,the number of longitudinal exploration of autonomous activities was significantly decreased,the DA level in the striatum and the number of TH immunopositive cells was decreased significantly,dopamine neurons was obviously impaired,the protein expressions ofα-Syn,COX-2 were up regulated significantly,the PGE2 level was increased(P<0.05 or P<0.01).Compared with Model group,Foshou San 100 mg/kg and 300 mg/kg could significantly decreased the time of the pole climbing test and the beam walk test,increased the numbers of longitudinal exploration time.It also raised the number of TH immune positive cells and reduced the protein expressions ofα-Syn and COX-2,and reduced PGE;content in substantia nigra.Conclusions:The potential therapeutic effect of Foshou San on PD may be related to reducingα-Syn and inhibiting MAO-B level.Nevertheless,the detailed molecular mechanism needs further study.
作者
曹方引
王强
宋文豪
曾丝丝
李丽
谭正怀
Cao Fangyin;Wang Qiang;Song Wenhao;Zeng Sisi;Li Li;Tan Zhenghuai(Chengdu Fifth People's Hospital,Chendu 611130;Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chendu 610075;Chengdu Fourth People's Hospital,Chendu 610036)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2022年第1期19-24,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
四川省中医药管理局重点学科建设项目(编号:2020ZDXK001)
