平颤颗粒治疗帕金森病的药效学研究

Pharmacodynamics of Pingchan Potion on Parkinson's Disease

目的:观察平颤颗粒对帕金森病(PD)模型鼠的行为及多巴胺能神经元的影响并探讨其治疗PD的作用机制.方法:运用6-羟基多巴胺两点注射法损毁大鼠右侧黑质致密部(SNC)和腹侧被盖区(VTA)多巴胺能神经元,制备PD模型,将模型成功大鼠随机分为模型组、美多芭组、平颤颗粒低、中、高剂量3组以及联合用药组,另设正常对照组,每组10只,分别给予相应处理,连续5wk观察各组大鼠处理前及处理后3,4,5wk行为学的变化,通过脑黑质酪氨酸羟化酶(TH)免疫组化染色观察多巴胺(DA)能神经元的损伤程度,并采用高效液相色谱法观察脑黑质DA及3,4-二羟基苯乙酸(DOPAC)含量变化.结果:平颤颗粒高、中剂量组大鼠的旋转次数多于美多芭组及联合用药组(P<0.05),但均少于模型组(P<0.05或P<0.01),模型组大鼠与治疗前比较旋转次数有显著增加(P<0.05),正常组大鼠行为则无变化;免疫组化检测显示平颤颗粒高、中剂量组黑质TH阳性神经元数目高于模型组,但低于正常组(P<0.05);高效液相色谱-电化学检测结果表明,各组大鼠中脑DA及DOPAC含量均低于正常组,平颤颗粒高、中剂量组低于联合用药组及美多芭组(P<0.05),而平颤颗粒低剂量组与模型组比较差异无显著性.结论:平颤颗粒能部分改善PD大鼠旋转行为,并减轻黑质细胞的受损程度,提高下降的DA水平,从而对PD起到治疗作用.

AIM： To observe the effects of Pingchan Potion on the rotation action and the dopaminergic neuron in Parkinson disease （PD） modal rats and explore the pharmacodynamics of Pingchan Potion. METHODS： PD model rats were established by microinjection of 6-hydroxydopamine solution into right ventral tegmental area （VTA） and substantia nigra pars compacta（SNC） of the mesencephslon. The 60 PD rats were divided randomly into six groups： model group, madopar group, Pingchan Potion （16, 8,4 g/kg） group and combined group. In addition, ten rats were included in the normal control group. All rats were continually treated for 5 weeks. The rotational behavior of rats before and after treatment by apomorphine was observed. After 5 weeks, the number of tymsine hydroxylase （TH） positive cells were detected by immunohistechemical method, and dopamine（DA） and its metabolic products in nigrostriatal system of each group were determined by using high-performance liquid chromatography coupled to electrochemical detection （HPLC-ECD）. RESULTS. Compared with model group, the times of rats rotation were decreased respectively after 3-week treatment in the madopar group and combined group（ P 〈 0.05 ） ; the times of rats rotation didn＇t decrease in Pingchan Potion 16 g/kg and 8 g/kg group, but it did not change obviously in 4 g/kg group （ P 〉 0.05 ） ; the times of rats rotation in model group increased post-treatmeat （ P 〈 0.05 ）, and the behaviour of normal group didn＇t change. The number of TH positive cells in substantial nigra of rats treated with Pingchan Potion 16 g/kg and 8 g/kg was higher than that of model group（ P 〈 0.05 ）, yet lower than that of normal group. The levels of DA and 3,4-dihydroxyphenylacetic acid （DOPAC） in the rats of Pingchan Potion （ 16, 8 g/kg） and madopar and combined groups were higher than that of the model group （ P 〈 0.05 ） , but lower than that of normal group, the levels of DA and DOPAC in Pingchan Potion 4 g/kg group did not significantly change. CONCLUSION： Pingchan Potion could partially improve the rotational behavior in PD model rats, and provide a protective effect against 6-OHDA -induced neuronal death in parkinsonian model by reducing DA neuron loss and increasing DA content.