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1、平颤颗粒治疗帕金森病药效学探究【摘要】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軽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,通过脑黑质酪氨酸務化酶(TH)免疫组化染色观察多巴胺(DA)
2、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3,4二軽基苯乙酸(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阳性神经元数目髙于模型组,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D0PAC含量均
3、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<;O.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.【关键词】帕金森病;平颤颗粒;旋转行为;酪氨酸单氧化酶;多巴胺[Abstract]AIM:ToobservetheeffectsofPingchanPotionontherotationactionandthedopaminergicneuroninParkinson
4、disease(PD)modelratsandexplorethepharmacodynamicsofPingchanPotion.METHODS:PDmodelratswereestablishedbymicroinjectionof6hydroxydopaminesolutionintorightventraltegmentalarea(VTA)andsubstantianigraparscompacta(SNC)ofthemesencephslon.The60PDratsweredivided
5、randomlyintosixgroups:modelgroup,madopargroup,PingchanPotion(16,8,4g/kg)groupandcombinedgroup.Inaddition,tenratswereineludedinthenormalcontrolgroup.Allratswerecontinuallytreatedfor5weeks.Therotationalbehaviorofratsbeforeandaftertreatmentbyapomorphinewa
6、sobserved.After5weeks,thenumberoftyrosinehydroxylase(TH)positivecellsweredetectedbyimmunohistochemicalmethod,anddopamine(DA)anditsmetabolicproductsinnigrostriatalsystemofeachgroupweredeterminedbyusinghighperformaneeliquidchromatographycoupledtoelectroc
7、hemicaldetection(HPLCECD).RESULTS:Comparedwithmodelgroup,thetimesofratsrotationweredecreasedrespectivelyafter3weektreatmentinthemadopargroupandcombinedgroup(P&It;0.05);thetimesofratsrotationdidntdecreaseinPingchanPotion16g/kgand8g/kggroup,butitdidnotch
8、angeobviouslyin4g/kggroup(P>;0.05);thetimesofratsrotationinmodelgroupincreasedposttreatmeat(P&It;0.05),andthebehaviourofnormalgroupdidntchange.ThenumberofTHpositivecellsinsubstantialnigraofra/tstreatedwithPingchanPotion16g/kgand8g/kgw