芍药苷对1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠黑质多巴胺能神经元保护作用及机制  

Protective effect and mechanism of paeoniflorin on dopaminergic neurons in substantia nigra of Parkinson’s disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

作　　者：荣华[1] 孙晓雪[1] 李晓明[1] 徐天娇[1] 李旭 郭科东 Rong Hua;Sun Xiaoxue;Li Xiaoming(Qiqihar Medical University,Qiqihar 161006)

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中国现代医药杂志》2022年第7期18-22,共5页Modern Medicine Journal of China

基　　金：2020年度黑龙江省省属高等学校基本科研业务费科研项目(编号:2020-KYYWF-004)。

摘　　要：目的探讨芍药苷对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠黑质多巴胺能神经元的保护作用及机制。方法C57BL/6小鼠随机分为对照组、模型组、司来吉兰组(10mg/kg)、芍药苷低剂量组(7.5mg/kg)和芍药苷高剂量组(30mg/kg),除对照组外其余各组采用MPTP(25mg/kg)腹腔注射给药7d,同时在注射结束1h后进行灌胃治疗,为期14d。通过爬杆、转棒实验观察小鼠的行为学变化,通过免疫组化实验检测小鼠黑质区域TH阳性细胞的表达水平,采用Annexin V-FITC双染法检测细胞凋亡率,通过分光光度法检测小鼠脑组织caspase-3酶活性,免疫印迹法检测α-突触核蛋白(α-syn)表达情况,实时定量PCR法检测α-syn基因的表达水平。结果与模型组比较,司来吉兰、芍药苷低、高剂量组可以显著缩短PD小鼠爬杆时间,延长小鼠在棒时间(P<0.05),提高TH阳性细胞的表达(P<0.05),抑制黑质多巴胺能神经元凋亡(P<0.05),减少caspase-3酶活性(P<0.05);司来吉兰及芍药苷高剂量组可显著降低α-syn蛋白及mRNA的表达(P<0.05)。结论芍药苷具有保护MPTP诱导的PD模型小鼠黑质多巴胺能神经元的作用,其机制可能与抑制α-syn表达有关。Objective To investigate the protective effect and mechanism of paeoniflorin on dopaminergic neurons in substantia nigra of Parkinson’s disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods C57BL/6 mice were randomly divided into control group,model group,selegiline group(10mg/kg),paeoniflorin low-dose group(7.5mg/kg)and paeoniflorin high-dose group(30mg/kg).Except for the control group,other groups were intraperitoneally injected with MPTP(25mg/kg)for 7 days,and intragastric administration was carried out 1h after the injection for 14 days.Climbing pole test and rotating rod test were used to observe the behavioral changes in the mice;the expression levels of TH positive cells in the substantia nigra region were determined by immunohistochemistry experiments;apoptosis of neurons was determined by Annexin V-FITC/PI staining.Caspase-3activity in the brain was determined by spectrophotometry and Western Blot technology was used to detect the expression of theα-syn protein,using fluorescence quantitative PCR technology to observe the expression of mRNAα-syn.Results Compared with the model group,selegiline and paeoniflorin could significantly prolong the residence time of mice and shorten the rod climbing time(P<0.05),increase the expression of TH positive cells(P<0.05),inhibit the apoptosis of dopaminergic neurons in the substantia nigra(P<0.05),and reduce the activity of caspase-3 enzyme(P<0.05);selegiline and paeoniflorin high-dose group can significantly reduce expression ofα-syn protein and mRNA(P<0.05).Conclusion Paeoniflorin can protect dopaminergic neurons in MPTP induced PD model mice,and its mechanism may be related to inhibitα-syn expression.

关 键 词：帕金森病 芍药苷 多巴胺能神经元 

分 类 号：R285[医药卫生—中药学]