“抗帕颗粒”对帕金森病模型鼠行为学的影响

Pharmaceutical effection of anti-Parkinson granule on the behavior of model rats with Parkinson disease

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）模型小鼠行为学的影响。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”（浓度800mg·mL-1）按40mg·kg-1·d-1灌胃，连续喂养4个月。比较分析各组、各时间点（15d、1个月、2个月、3个月、4个月）爬杆实验、悬挂实验、游泳实验等行为学评分情况。结果①各组实验动物存活情况，正常对照组30只最终均存活，PD模型对照组4个月时存活27只，PD模型干预组4个月时存活28只；②各组爬杆实验分值情况：正常对照组与PD模型对照组比较，各时间点评分均P〈0．01。正常对照组与PD模型干预组比较，15d、1个月时均P〈0．01，2、4个月时P〈0．05，3个月时P〉0．05。PD模型对照组与PD模型干预组比较，15d、1个月时，均P〉0．05，2、4个月时，P〈0．05，3个月时，P〈0．01。PD模型干预组各时间点分值比较，15d评分较1个月时，P〉0．05，较2月时，P〈0．05，较3、4个月时均，P〈0．01；1个月评分较2个月时，P〈0．05，较3、4个月时均，P〈0．01；2个月评分较3、4个月时均，P〈0．05；3个月评分较4个月时，P〉0．05；③各组悬挂实验分值情况，正常对照组与PD模型对照组比较，各时间点评分均P〈0．01。正常对照组与PD模型干预组比较，15d、1个月时均P〈0．01，2、3、4个月时均P〈0．05。PD模型对照组与PD模型干预组比较，15d、1个月时均P〉0．05，2个月时P〈0．05，3、4个月时均P〈0．01。PD模型干预组各时间点分值比较，15d评分较1个月时P〉0．05，较2、3、4个月时均P〈0．05；1个月评分较2、3、4个月时均P〈0．05；2个月评分较3、4个月时均P〉0．05；3个月评分较4个月时P〉0．05；④各组游泳实验分值情况：正常对照组与PD模型对照组比较，各时间点评分P均〈0．01。正常对照组与PD模型干预组比较，15d、1个月时均P〈0．01，2、3、4个月时均P〈0．05。PD模型对照组与PD模型干预组比较，15d、1个月、2个月时均P〉0．05，3、4个月时P均〈0．01。PD模型干预组各时间点分值比较，15d评分较1个月、2个月时均P〉0．05，较3、4个月时均P〈0．05；1个月评分较2个月时P〉0．05，较3、4个月时均P〈0．05；2个月评分较3、4个月时均P〈0．05；3个月评分较4个月时P〉0．05。结论“抗帕颗粒”对MPTP诱发的C57BL／6小鼠PD模型行为学具有良好的改善作用；但起效较慢，至2-3个月左右开始显现疗效；在应用过程中应注意足量、足程等问题，以保证其作用的有效性、持久性。另外，“抗帕颗粒”对游泳动作的改善相对较慢，需要更持久、更足量的治疗，显示中药制剂作用的缓慢性和局限性，提示联合使用多巴制剂中西医结合治疗PD的必要性。

Objective To explore the effection of anti-Parkinson granule＇s pharmaceutical on the behavior of model rats with 1,2, 3, 6-tetrahydro-l-methyl-4-phenylpyridine （ MPTP ） Parkinson disease （ PD ）. Methods Randomly divide 90 healthy male C57BL/6 mice, 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 was 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 ） ; The PD model intervention group was pumped stomach with anti-Parkinson granule solution（ 800mg ·mL-1 ,40mg · kg-1 · d-1 ） .All groups were feed continually for 4 months. The behavioral scores of each group in the test of pole test, traction test and swim test at different point-in-time（ 15d, 1 month, 2 months, 3 months, 4 months） would be comparatively analyzed. Results （1） Surviving condition of each group ： 30 mice of the normal control group all survived eventually. After 4 months, 27 mice of the PD model control group and 28 mice of the PD model intervention group survived. （2） Scores of each group in pole test： there were significant differences between the normal control group and the PD model control group at all points-in-time （ all values P 〈 0.01 ）. Meanwhile, between the normal control group and the PD model intervention group, there were great differences at the 15d, 1, 2 and 4 months （P〈0.01 at 15d, 1 month and P〈0.05 at 2, 4 months） and no difference at the 5 months（P〉0.05）. Between the PD modal control group and the PD model intervention group, there were obvious differences at the 2, 3 and 4 months （P〈0.05 at the 2,4 months, P〈0.01 at the 3 months） while there were no differences at the 15d, 1 month （P〉0.05）. The scores of each point-in-time in the PD model intervention group were contrasted as follows： no difference was found between 15d and 1 month, and 15d vs 2 months （P〈0.05）, 15d vs 3,4 months （P〈0.01） ; great significances were shown between the 1 month and 3, 4 months （ P〈0.01 ）, and 1 month vs. 2 months P〈 0.05 ; 2 months vs. 3, 4 months （ P〈 0.05 ） ; 3 months vs. 4 months P〈0.05. （3） Scores of each group in traction test： there were significant differences between the normal control group and the PD model control group at all points-in-time（ all values P〈0.01 ）. Between the normal control group and the PD model intervention group, there was great significance at 15d and 1 month （P〈0.01） and significance at 2,3 and 4 months （P〈0.05）. Between the PD model control group and the PD model intervention group, there were obvious differences at 2 months （P〈0.05）, 3 months and 4 months （P〈0.01） while there were no differences at 15d, 1 month. The scores of each point-in-time in the PD model intervention group were contrasted as follows ： no difference was found in the 15d vs.1 month, but 15d vs.2,3and 4 months P〈0.05; The great significances were shown between 1 month vs.2 months, 1 month vs.3 months, 1 month vs.4 months （P〈0.05） ;and 2 months vs.3 months, 2 months vs.4 months were all P〉0.05; 3 months vs.4 months was also P〉0.05. （4） Scores of each group in swim test： there were significant differences between the normal control group and the PD model control group at all points-in-time（ all values P〈 0. 01 ）. Between the normal control group and the PD model intervention group, there were great significances at 15d and 1 month （P〈0.01） and significances at 2,3 and 4 months （P〈0.05）. Between the PD model control group and the PD model intervention group, there were obvious differences at 3 months and 4 months （P〈O.01） while there were no differences at 15d, 1 month and 2 months （P〉0.05）. The scores of each point-in-time in the PD model intervention group were contrasted as follows： no difference was found in 15d vs. 1 month, 15d vs.2 months, but 15d vs.3 months and 15d vs.4 months P〈0.05; 1 month vs.2 months and 3 months vs.4 months P〉0.05, great significances were shown among 1 month vs.3 months, 1 month vs. 4 months, 2 months vs. 3 months, 2 months vs.4 months （P〈0.05）. Conclusion Anti-Parkinson granule is an effective recipe in recovering the C57BL/6 PD model mice evoked by MPTP, and it appears to work from 2 to 3 months which shown its slow action. Therefore, the treatment with adequate dosage and duration should be carried out to ensure the effection and durability during the clinical application of anti-Parkinson granule. Furthermore, the improved performance for swim treated by anti- Parkinson granule is relatively slow, which needs the treatment with more dosage and duration. Because of the moderation and limition of the traditional Chinese medicine, the integrated Chinese-Western therapy by combination using of Levodopa in the treatment of PD is necessary.