摘要
目的 探讨“抗帕颗粒”对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）帕金森病（PD）模型小鼠黑质纹状体区α-突触共核蛋白（α-syn）异常聚集的影响。方法 90只健康雄性C57BL/6小鼠，鼠龄8~12w。随机分为3组，正常对照组30只、PD模型对照组30只、PD模型干预组30只。MPTP腹腔注射40mg·Kg-1·d-1×7制备小鼠PD模型；正常对照组及PD模型对照组予生理盐水1ml·d-1灌胃；PD模型干预组给予“抗帕颗粒”40mg·kg-1·d-1灌胃，连续喂养4个月。比较分析各组4月时黑质纹状体区α-syn聚集情况。结果 ①正常对照组30只（30/30只）最终均存活，PD模型对照组4个月时存活27只（27/30只），PD模型干预组4个月时存活28只（28/30只）；②PD模型对照组、PD模型干预组小鼠每次注射MPTP后，先有短暂兴奋（持续7.61±2.17min），表现为四处窜跳；随即出现全身中重度震颤，皮毛及尾巴时有竖立，活动减少，持续24.23±3.89min后震颤消失；随后出现活动减少；③黑质纹状体区α-syn免疫荧光双染检测；③PD模型对照组较正常对照组明显增多，PD模型干预组较PD模型对照组有所减少，但仍较正常对照组增多；④Westernblotting检测α-syn蛋白量的表达，正常对照组与PD模型对照组比较，P<0.001；与PD模型干预组比较，P<0.001；PD模型对照组与PD模型干预组比较，P<0.05。结论 “抗帕颗粒”对PD小鼠黑质纹状体区α-syn异常聚集具有一定程度的抑制作用，阻断氧化应激反应可能是这种保护作用的关键机制，有望改善PD治疗现状并在临床进一步推广应用。
Objective To explore the effect of "anti-Parkinson granule" on synaptic nigrostriatal areaá-synuclein( á-syn) anomaly aggregation in methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP) Parkinson'sdisease( PD) model mice. Method Randomly divided 90 healthy male C57BL/6mice, with ages arrange 8-12 weeks,into 3 groups including of the normal control group, the PD model control group and the PD model intervention group,each have 30 mice. The PD model group were made through intraperitoneal injection with MPTP(40mg·kg-1·d-1×7).The normal control group and the PD model control group were pumped stomach with normal saline( 1ml·d-1); ThePD model intervention group were pumped stomach with anti-Parkinson granule solution(40mg·kg-1·d-1), andwere fed continually for 4 months . At the end of the forth month, contrasted and analysised each group's status onaccumulation of α-syn. Results ① 30 mice(30/30 mice)were survival in the normal control group; the PD modelcontrol group at end of 4 months survived 27 mice(27/30 mice); and the PD model intervention group at end of 4months survived 28 mice(28/30 mice). ② After injection with MPTP, mice of the PD model control group and thePD model intervention group had short excitements( duration 7.61±2.17 min), behaved jumping around, followedwith the whole body's moderate or severe tremors, fur and tails erected timely, less movement. Tremors ceased after24.23±3.89 min, and then movement became less. ③ α-syn double immunofluorescence staining in Nigrostriatalarea of PD model group increased significantly compared with that of normal control group, α-syn of the interventiongroup decreased compared with that of the PD model group, but still showed an increase compared with that of thecontrol group. ④ Western blotting was used to detect the expression of α-syn protein. The results showed that therewere significantly difference between the normal control group and PD model group(P<0.001) , also with PD modelintervention group P<0.001, there were significantly difference between PD model group and PD intervention modelgroup(P<0.05) . Conclusion " anti-Parkinson granule " could inhibit in certain degree the abnormal α-synaggregation on PD mouse nigrostriatal area. The key mechanism of this protective effect may be through blocking theoxidative stress. It would be applicable to improve the situation of PD treatment in further clinical application.
作者
赵晓晖
朱玉萍
杨娟
刘慧琴
沈建
ZHAO Xiao-hui;ZHU Yu-ping;YANG Juan;LIU Hui-qin;SHEN Jian(Department of Neurology, the People's Hospital of Pudong, Shanghai 201200, China)
出处
《脑与神经疾病杂志》
2016年第10期612-617,共6页
Journal of Brain and Nervous Diseases
基金
上海市自然科学基金项目(13ZR1437400)
关键词
帕金森病
MPTP
小鼠模型
“抗帕颗粒”
α-
突触共核蛋白
Parkinson's disease
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Mouse model
Anti-Parkinson granule
α-synuclein
