和厚朴酚在帕金森病小鼠模型中的神经保护作用

Neuroprotective effects of honokiol on mouse model with Parkinson's disease

目的探讨和厚朴酚在帕金森病小鼠模型中的神经保护作用及可能的机制。方法1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导建立帕金森病小鼠模型。随机将60只C57BL/6雄性小鼠均分为对照组、MPTP模型组、金刚烷胺组(阳性对照,40mg/kg)、和厚朴酚A组(10mg/kg)、和厚朴酚B组(30mg/kg)。观察各组小鼠一般行为的差异,通过自主活动实验测定每只小鼠5min内的活动次数,采用高效液相-电化学法(HPLC-EC)检测小鼠脑内纹状体多巴胺的变化。结果①腹腔给予MPTP(30mg/kg)后5min,小鼠出现暂时性躯干震颤、竖毛、尾巴过伸、动作减少等不自主运动,可以判定帕金森病模型复制成功。②MPTP模型组小鼠5min的自主活动次数(102±7次)低于对照组(583±11次,P<0.01),纹状体多巴胺含量(2.10±0.03nmol/g)较对照组(8.72±0.14nmol/g)明显降低(P<0.01)。③和厚朴酚(10、30mg/kg)预处理能明显改善小鼠异常的行为学表现。和厚朴酚A、B组小鼠自主活动次数(分别为301±13、377±11次)较模型组(102±7次)明显增加(P<0.05);和厚朴酚A、B组小鼠脑内多巴胺的含量(分别为3.77±0.08、5.22±0.11nmol/g)也较模型组(2.10±0.03nmol/g)明显增加(P<0.01)。结论和厚朴酚具有神经保护作用,能对抗MPTP诱导的帕金森病模型小鼠的神经损伤,其机制可能与和厚朴酚能营养神经元,促多巴胺能神经元存活、分化和生长,从而部分恢复多巴胺的合成、代谢有关。

Objective To explore the neuroprotective effect of honokiol against Parkinson＇s disease（PD）in mouse model,and investigate the possible mechanism involved.Methods 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）was injected into abdominal cavity of mouse to establish the PD model.Sixty C57BL/6 male mice were randomly allocated into five groups：control group,MPTP model group,amantadine group（positive control,40mg/kg）,honokiol group A（10mg/kg）and honokiol group B（30mg/kg）.Spontaneous movement test was used to measure the activity frequency of each mouse in 5 minutes.The technique of high performance liquid chromatography-electrochemistry was utilized to detect the changes of dopamine（DA）contents in mouse striatum.Results a）Since the involuntary movement appeared,such as trunk trembling,piloerection,tail extending and movement reduction,the PD model was regarded as having been reproduced successfully.b）The spontaneous movement frequency in 5 minutes of the mice in MPTP model group（102±7）was lower than that in the control group（583±11,P〈0.01）.Compared to the control group（8.72±0.14nmol/g）,the DA content in striatum of the mice in MPTP model group（2.10±0.03nmol/g）was significantly degraded.c）The abnormal behavior of the mice in honokiol groups A and B was rectified obviously,and the spontaneous movement frequency in five minutes of the mice in the both groups（301±13 and 377±11）was significantly increased（P〈0.05）compared to that in model group（102±7）;the DA contents in striatum of the mice in the both groups raised significantly（3.77±0.08 and 5.22±0.11nmol/g）compared to that in model group（2.10±0.03nmol/g,P〈0.01）.Conclusions The results of present study suggest that honokiol has neuroprotective effect on MPTP-induced neuron impairment.The possible mechanisms may be related with the restoration of the synthesis,metabolic effects of honokiol on neurons.