哌替啶类衍生物造模帕金森病小鼠的最佳剂量

Optimal dosage of pethidine derivative in establishing mice model of Parkinson disease

目的:比较不同剂量哌替啶类衍生物1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine,MPTP)建立的帕金森病小鼠模型对小鼠纹状体多巴胺含量的影响。方法:实验于2003-11/2004-07在北京宣武医院神经生物学实验室完成。选择C57BL/6L小鼠60只,采用不同剂量MPTP建立帕金森病小鼠模型,随机分6组,MPTP40mg/kg皮下注射1次组10只;MPTP20mg/kg腹腔注射,每2h1次,注射3次组10只;MPTP25mg/kg腹腔注射,每2h1次,注射3次组10只;MPTP45mg/kg皮下注射1次组10只;MPTP35mg/kg皮下注射1次组10只;正常对照组10只。采用Lowry法测定纹状体组织中多巴胺含量/蛋白质含量。结果:纳入动物60只,52只进入结果分析,其中8只均在处死前死亡。MPTP使小鼠纹状体多巴胺含量显著性下降。正常对照组多巴胺含量为(136.39±41.61)μg/g;MPTP35,40,45mg/kg皮下注射1次组分别为(107.97±26.92),(85.91±24.60),(74.13±12.49)μg/g,分别是正常对照组的79.16%,62.99%,54.35%;MPTP20,25mg/kg腹腔注射每2h1次,注射3次组分别为(44.90±18.41),(44.30±29.44)μg/g,分别是正常对照组的32.92%,32.48%。5个模型组与正常对照组比较差异均显著(P<0.01)。结论:MPTP20mg/kg腹腔注射每2h1次,注射3次和MPTP40mg/kg皮下注射1次两种模型是对帕金森病不同研究方向的理想模型。

AIM： To study the effect of different dosages of pethidine derivative 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine （MPTP） on content of dopamine in corpus striatum of mice with Parkinson disease （PD）. METHODES： The experiment was completed in the Neurobiological Laboratory of Beijing Xuanwu Hospital from November 2003 to July 2004. Totally 60 C57BL/6 L mice were selected to establish PD models on the basis of various dosages and divided randomly into 40 mg/kg MPTP group with hypodermic injection for once, 20 mg/kg MPTP group with intraperitoneal injection for 3 times of 2 hour/time, 25 mg/kg MPTP group with intraperitoneal injection for 3 times of 2 hour/time, 45 mg/kg MPTP group with hypodermic injection for once, 35 mg/kg MPTP group with hypodermic injection for once, and normal control group with 10 in each group. Content of dopamine/protein in corpus striatum was assayed With Lowry method. RESULTS： Totally 60 animals were selected in the study, but 8 died before sacrifice. Therefore, 52 rats entered the final analysis. MPTP could decrease content of dopamine in corpus striatum obviously. Content of dopamine was （136.39±41.61） μg/g in normal control group and （107.97 ±26.92）, （85.91±24.60）, （74.13±12.49） μg/g in 35, 40 and 45 MPTP group with hypodermic injection for once, which was of 79.16%, 62.99% and 54.35% as the controls respectively. Content of dopamine was （44.90±18.41）, （44.30±29.44） μg/g in 20 and 25 mg/kg MPTP group with intraperitoneal injection for 3 times of 2 hour/time, which was of 32.92% and 32.48% as the controls respectively. There was no significant difference among 5 model groups and normal control group （P 〈 0.01）. CONCLUSION： Models of 20 mg/kg MPTP with intraperitoneal injection tor 3 times of 2 hour/time and 40 mg/kg MPTP with hypodermic injection for once are ideal for treating PD in different researching ways.