两种帕金森病模型黑质一氧化氮合酶mRNA的表达及灵芝孢子油的调控作用

目的：对比研究1-甲基-4苯基-1，2，3，6-四氢吡啶（MPTP）小鼠模型和6-羟基多巴（6-OHDA）大鼠模型黑质区诱导型一氧化氮合酶（iNOS）mRNA表达水平的变化，探讨灵芝孢子油对两种帕金森病模型黑质区iNOS mRNA表达的调节作用.方法：分别建立MPTP小鼠模型，C57BL小鼠分为MPTP组、灵芝孢子油＋MPTP组、正常对照组.MPTP组皮下注射MPTP共6 d，灵芝孢子油＋MPTP组在注射MPTP前2 d开始鼻饲灵芝孢子油，连续8 d，MPTP组喂食生理盐水做对照，2周后断头取中脑腹侧组织.6-OHDA大鼠模型，SD大鼠分为6-OHDA组、灵芝孢子油＋6-OHDA组、正常对照组.用脑部立体定向法将6-OHDA注射到SD大鼠一侧黑质致密部建立大鼠帕金森病模型，灵芝孢子油组在造模前3 d开始给药，连续10 d.6-OHDA组喂食生理盐水做对照.造模后第13天取各组大鼠中脑腹侧组织，用荧光半定量RT-PCR法检测各组中脑腹侧iNOS mRNA表达量.结果：MPTP模型中，MPTP组的iNOS mRNA表达量比正常对照组增高，灵芝孢子油组iNOS mRNA表达量比正常对照组减少，组间两两比较差异有显著性.6-OHDA模型中，6-OHDA组的iNOS mRNA表达量比正常对照组略增多，灵芝孢子油组iNOS mRNA的表达量无明显改变.两处理组组间比较无明显差异.结论：MPTP模型黑质区iNOS mRNA表达量明显增高，提示iNOS mRNA的过度表达可能与MPTP的发病机制有关，灵芝孢子油能有效下调iNOS mRNA的高表达.     

低压低氧对帕金森病模型小鼠学习记忆能力的影响

目的探讨低压低氧环境下帕金森病（PD）模型小鼠学习记忆能力的变化。方法 60只SPF级雄性昆明小鼠,体质量17-22 g。随机分为1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）组（PD模型组）、低压低氧（HH）组、MTPT＋HH组和对照组,每组15只。以动物实验用高原环境模拟舱模拟低压低氧环境,通过腹腔注射MPTP诱导PD模型小鼠,使用Y型-电迷宫和跳台实验评价小鼠学习记忆能力。结果与对照组比较,MPTP组、HH组和MPTP＋HH组Y型-电迷宫学习和记忆总反应时间（TRT）明显延长（P均〈0.01）,错误反应次数（EN）明显增多（P均〈0.01）;跳台实验学习和记忆TRT明显延长（P均〈0.01）,EN明显增多（P均〈0.01）。且上述各指标MPTP＋HH组分别低于MPTP组与HH组（P均〈0.05）,而MPTP组与HH组之间水平相近（P均〉0.05）。结论低压低氧加重了MPTP所致PD模型小鼠学习记忆能力的下降程度。     

不同周龄组的C57BL小鼠多巴胺神经元对MPTP敏感性的对比及其机制探讨

目的：观察不同周龄的C57BL小鼠多巴胺神经元对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）的药物敏感性差异，探讨其差异的机制是否与热休克蛋白70（HSP70）不同表达相关。方法：将4。6周龄及15。17周龄的C57BL小鼠给予MPTP造成帕金森病模型，同时设立对照组。采用高效液相法检测纹状体内多巴胺（DA）、3，4-二羟苯乙酸（DOPAC）、高香草酸（HVA）的含量。免疫组化法观察黑质中酪胺酸羟化酶（TH）阳性细胞及HSP70的表达。结果：15-17周龄小鼠在MPTP造模后纹状体中DA、DOPAC、HVA的含量，黑质中的TH阳性细胞数和HSP70的表达含量均明显低于4—6周龄模型组（P〈0．05），而两个周龄的对照组的各项指标均无明显差异。结论：15-17周龄的C57BL小鼠对于MPTP的敏感性明显高于4—6周龄小鼠。HSP70的表达量不同可能是造成敏感性差异的原因之一。     

耐力训练对帕金森模型小鼠中脑线粒体自噬相关基因表达的影响

目的:探讨耐力训练对帕金森病(PD)模型小鼠中脑线粒体自噬的影响,揭示运动预防帕金森病的分子生物学机制。方法:10周龄雄性C57BL/6小鼠32只,随机分为安静组(C),运动组(E),帕金森模型安静组(P)及帕金森模型运动组(PE),每组8只。E组及PE组小鼠进行为期8周跑台耐力训练,跑台速度15m/min,坡度为0%,每天运动持续50min,每周6次,周日休息。训练结束后,P组和PE组小鼠腹腔注射MPTP(30mg/kg),C组和E组小鼠注射等量生理盐水,持续3d。注射结束1周后,处死各组小鼠,取双侧中脑及纹状体,采用实时PCR及Western blot技术检测线粒体自噬相关基因及TH蛋白表达,HPLC技术检测中脑及纹状体组织内DA含量。结果:与C组比,E组小鼠中脑TH蛋白上调(P0.05),中脑及纹状体DA含量均增加(P0.05),P组和PE组小鼠TH蛋白及DA含量均显著下降(P0.01),而P组较PE组相应指标下降更明显(P0.05)。与C组比,E组小鼠中脑PINK、PARK2 m RNA及PINK1蛋白表达上调(P0.05),LC3Ⅱ/Ⅰ比值增加,P组小鼠PINK1m RNA表达下调(P0.05),PE组小鼠PINK1 m RNA、Parkin蛋白含量及LC3Ⅱ/Ⅰ比值较P组增加。结论:为期3d的MPTP处理可导致小鼠中脑及纹状体TH及DA含量下降,诱导帕金森病发生,耐力训练可缓解这一现象;MPTP诱导的帕金森小鼠模型中脑线粒体自噬水平下降,而耐力训练可作用于线粒体自噬相关基因的表达,抑制MPTP的神经毒性作用。     

帕金森病模型小鼠的行为学特征及其检测方法研究

帕金森病是一种常见的神经系统退变性疾病,其主要是由于黑质多巴胺能神经元坏死、凋亡,细胞数目减少,使黑质-纹状体通路多巴胺释放减少,患者出现静止性震颤、肌张力增高、运动减少等一系列症状。目前已建立多种帕金森病动物模型,其中1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)致帕金森病小鼠模型是目前最常用的帕金森病动物模型之一,其许多行为学特征与帕金森病患者临床表现类似,通过多种方法对其行为学特征进行检测,了解其行为学特征与生理病理的关系,将为帕金森病的病因病理研究提供有效的途径。     

烟酰胺对帕金森病小鼠黑质细胞凋亡的影响

目的:探讨黑质细胞凋亡在帕金森病发病机制中的作用及烟酰胺对帕金森病小鼠黑质细胞凋亡和Bax蛋白表达的影响。方法:给C57BL小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备帕金森病小鼠模型。利用原位缺口末端标记法(TUNEL)及Bax免疫组化方法观察黑质细胞凋亡情况及烟酰胺干预的影响。结果:帕金森病小鼠黑质致密带可见大量凋亡细胞犤(19.43±3.33)个/视野犦Bax蛋白表达(Bax阳性细胞平均灰度值80.59±3.73)。预先应用烟酰胺能使凋亡细胞减少犤(6.33±2.35)个/视野犦,烟酰胺 MPTP组与MPTP组间比较差异有显著性意义(q=9.23,P<0.05)。预先应用烟酰胺也能使Bax蛋白表达降低(Bax阳性细胞平均灰度值107.59±2.50),烟酰胺 MPTP组与MPTP组间比较差异有显著性意义(q=7.44,P<0.05)。结论:烟酰胺可降低MPTP诱导的C57BL小鼠黑质细胞Bax蛋白表达,减少黑质细胞凋亡。     

哌替啶类衍生物造模帕金森病小鼠的最佳剂量

目的：比较不同剂量哌替啶类衍生物1-甲基-4-苯基-1,2，3，6-四氧吡啶（1-methy-4-phenyl—1，2，3，6-tetrahydropyfindine，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建立帕余森病小鼠模型，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。正常埘照组多巴胺含量为（136．39&;#177;41．61）μg/g；MPTP35，40，45mg／kg皮下注射1次组分别为（107．97&;#177;26．92），（85．91&;#177;24．60），（74．13&;#177;12．49）μg/g，分别是正常对照组的79．16％，62．99％，54．35％；MPTPP20，25mg／kg腹腔注射每2h1次，注射3次组分别为（44．90&;#177;18.41），（44．30&;#177;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。     

环氧合酶2表达对帕金森病模型小鼠黑质细胞凋亡的影响

目的:观察环氧合酶2表达对帕金森病模型小鼠中脑黑质细胞凋亡的影响。方法:实验于2005-01/08在华北煤炭医学院解剖学教研室实验室完成。健康雄性C57BL/6N小鼠45只随机分为3组,每组15只。①模型组:皮下注射神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine,MPTP)(30mg/kg,盐水溶),1次/d,连续5d。②环氧合酶2抑制剂组:在MPTP注射前3d经口给予环氧合酶2抑制剂Celecoxib(250mg/kg),1次/d,连续3d,随后在每天注射MPTP前3.0h给予1次Celecoxib,连续5d。③对照组:注射与模型组等体积生理盐水。所有动物于最后一次注射后24h处死。通过免疫组织化学和免疫蛋白印记法,观察帕金森病模型小鼠多巴胺能神经元数量和黑质环氧合酶2、半胱氨酸天冬氨酸蛋白酶3和多(ADP-核糖)聚合酶免疫反应阳性细胞数量的变化及腹侧中脑环氧合酶2、凋亡蛋白酶活化因子1和半胱氨酸天冬氨酸蛋白酶3表达水平的变化;观察给予环氧合酶2抑制剂Celecoxib后对上述变化的影响。结果:与对照小鼠相比,模型组小鼠多巴胺能神经元数量下降约63%(P<0.01),黑质环氧合酶2、半胱氨酸天冬氨酸蛋白酶3和多(ADP-核糖)聚合酶免疫反应阳性细胞数量增加(P<0.01),腹侧中脑环氧合酶2、凋亡蛋白酶活化因子1和半胱氨酸天冬氨酸蛋白酶3表达水平大幅升高(P<0.01)。环氧合酶2抑制剂组小鼠黑质多巴胺能神经元数量仅较对照组下降约37%(P<0.01)。与模型组小鼠比较,黑质环氧合酶2、半胱氨酸天冬氨酸蛋白酶3和多(ADP-核糖)聚合酶免疫反应阳性细胞数量减少(P<0.01),腹侧中脑环氧合酶2、凋亡蛋白酶活化因子1和半胱氨酸天冬氨酸蛋白酶3表达水平明显下降(P<0.01)。结论:帕金森病小鼠黑质细胞凋亡可能与环氧合酶2表达有关;环氧合酶2抑制剂Celecoxib对帕金森病小鼠具有神经保护作用。     

帕金森病研究的热点：3-硝基丙酸预处理对多巴胺能神经元的保护作用

背景：3-硝基丙酸可以抑制氧化磷酸化过程，损害细胞的能量代谢从而引起细胞的损伤。但是小剂量的3-硝基丙酸却可以通过轻度抑制细胞的氧化磷酸化过程。激发细胞内源性保护因子保护神经元，增加神经元对缺血缺氧的耐受性，但它对多巴胺能神经元是否也有类似的作用尚不十分清楚。目的：探讨3-硝基丙酸预处理能否增强多巴胺能神经元对1-甲基-4苯基吡啶离子毒性的耐受。设计：以能分泌多巴胺的神经母细胞瘤SH-SY5Y细胞为研究对象，进行随机对照的探索性研究。单位：一所大学附属医院的神经科。材料：实验于2003—03／11在同济医学院病理生理实验室完成。SH—SY5Y细胞购于北京协和医科大学细胞典藏中心。干预：细胞随机分为6组，将1-甲基-4苯基吡啶离子加入到培养的多巴胺能神经元SH-SY5Y细胞中制作帕金森病的细胞模型，在加入1-甲基-4苯基吡啶离子(0．25mmol／L)前，分别单次或多次加入3-硝基丙酸(0．2mmol／L)形成预处理，应用四氮唑盐检测细胞生存率，[^3H]DA摄取率测定多巴胺能细胞突触前功能。主要观察指标：主要结局：细胞生存率。次要结局：[^3H]DA摄取率。结果：1-甲基-4苯基吡啶离子组细胞生存率(54．3％)较空白对照组明显降低(P&;lt;0．01)，3-硝基丙酸预处理后，细胞生存率明显增高，分别为71．8％(单次)，85．2％(多次)，单次预处理组与多次预处理组相比也有显著性差异(P&;lt;0．05)。[^3H]DA摄取率结果与细胞生存率结果相似。[^3H]DA摄取率分别为65．8％(单次)，80．3％(多次)，较1-甲基-4苯基吡啶离子组(50．1％)明显提高，且多次预处理较单次预处理效果更好。单加3-硝基丙酸对细胞无影响。结论：3-硝基丙酸预处理可明显增强多巴胺能神经元对1-基-4苯基吡啶离子毒性作用的耐受性，对多巴胺能神经元有明显的保护作用，多次预处理的保护作用更加显著。     

哌替啶类衍生物造模帕金森病小鼠的最佳剂量

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。     

神经干细胞移植对帕金森病鼠纹状体多巴胺含量的影响

目的观察神经干细胞定向移植后对帕金森鼠纹状体多巴胺含量的影响,证实神经干细胞移植治疗的可行性。方法建立帕金森病模型大鼠以及体外培养神经干细胞,然后将神经干细胞悬液立体定向移植到帕金森病模型鼠黑质纹状体区,测定纹状体的多巴胺含量,并与生理盐水组和非移植组相比。结果神经干细胞移植后帕金森病模型鼠纹状体多巴胺含量(346±26)μg/g与生理盐水组(58±56)μg/g和非移植组(72±60)μg/g比较明显增多,经t检验差异有显著性意义(t=13.99,12.57,P<0.05)。结论神经干细胞移植能减轻6-羟基多巴胺对黑质纹状体多巴胺能神经元的损伤。     

茶多酚对1-甲基-4-苯基吡啶离子诱导的PC12细胞损伤的保护作用

目的：探讨茶多酚（TP）对1-甲基-4-苯基吡啶离子（MPP^＋）诱导的帕金森病细胞模型的保护作用及机制。方法：将MPP＋或TP加入培养的PCI2细胞,四甲基偶氮唑盐法检测细胞活性及代谢状态,荧光法测定细胞内活性氧（ROS）水平,流式细胞术检测细胞凋亡率,RT-PCR法检测bcl-2基因mRNA表达,比较各组的差异。结果：与MPP＋组相比TP＋MPP＋组细胞存活率明显升高,凋亡率、ROS水平明显降低,bcl．2mRNA表达升高。结论：TP可通过抗氧化及抗凋亡机制保护PCI2细胞免于MPP^＋的损伤     

Aerobic Exercise: Evidence for a Direct Brain Effect to Slow Parkinson Disease Progression

No medications are proven to slow the progression of Parkinson disease (PD). Of special concern with longer-standing PD is cognitive decline, as well as motor symptoms unresponsive to dopamine replacement therapy. Not fully recognized is the substantial accumulating evidence that long-term aerobic exercise may attenuate PD progression. Randomized controlled trial proof will not be forthcoming due to many complicating methodological factors. However, extensive and diverse avenues of scientific investigation converge to argue that aerobic exercise and cardiovascular fitness directly influence cerebral mechanisms mediating PD progression. To objectively assess the evidence for a PD exercise benefit, a comprehensive PubMed literature search was conducted, with an unbiased focus on exercise influences on parkinsonism, cognition, brain structure, and brain function. This aggregate literature provides a compelling argument for regular aerobic-type exercise and cardiovascular fitness attenuating PD progression.     

Voltage-gated calcium channels and Parkinson's disease

A complex interaction of environmental, genetic and epigenetic factors combine with ageing to cause the most prevalent of movement disorders Parkinson's disease. Current pharmacological treatments only tackle the symptoms and do not stop progression of the disease or reverse the neurodegenerative process. While some incidences of Parkinson's disease arise through heritable genetic defects, the cause of the majority of cases remains unknown. Likewise, why some neuronal populations are more susceptible to neurodegeneration than others is not clear, but as the molecular pathways responsible for the process of cell death are unravelled, it is increasingly apparent that disrupted cellular energy metabolism plays a central role. Precise control of cellular calcium concentrations is crucial for maintenance of energy homeostasis. Recently, differential cellular expression of neuronal voltage-gated calcium channel (Ca_V) isoforms has been implicated in the susceptibility of vulnerable neurons to neurodegeneration in Parkinson's disease. Ca_V channels are also involved in the synaptic plasticity response to the denervation that occurs in Parkinson's disease and following chronic treatment with anti-parkinsonian drugs. This review will examine the putative role neuronal Ca_V channels have in the pathogenesis and treatment of Parkinson's disease.     

High affinity of 4-(4-(dimethylamino)styryl)-N-methylpyridinium transport for assessing organic cation drugs in hepatocellular carcinoma cells

Human organic cation transporter 1 (hOCT1) and human organic cation transporter 3 (hOCT3) are highly expressed in hepatocytes and play important roles in cationic drug absorption, distribution, and elimination. A previous study demonstrated that downregulation of hOCT1 and hOCT3 mRNA was related to hepatocellular carcinoma (HepG2) prognosis and severity. Whether these transporters expressed in HepG2 cells serve for cationic drug delivery has not been investigated. Besides radioactive transport, options for assessing hOCTs in hepatocytes are limited. This study clarified the significant roles of hOCTs in HepG2 by comparing cationic fluorescent 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP⁺) with traditional [³H]-1-methyl-4-phenylpyridinium (MPP⁺). The results showed ASP⁺ was preferably transported into HepG2 compared to [³H]-MPP⁺ with high affinity and a high maximal transport rate. Selective transport of ASP⁺ mediated by hOCTs was influenced by extracellular pH, temperature, and membrane depolarization, corresponding to hOCT1 and hOCT3 expressions. Furthermore, transport of cationic drugs, metformin, and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions. The fluorescent ASP⁺-based in vitro model may also provide a rapid and powerful analytical tool for further screening of cationic drug actions and interactions with hOCTs, particularly hOCT1 and hOCT3 in hepatocellular carcinoma.     

6r,a novel oxadiazole analogue of ethacrynic acid,exhibits antitumor activity both in vitro and in vivo by induction of cell apoptosis and S-phase arrest

This study investigated the in vitro and in vivo antitumor effects of 5-[2,3-Dichloro-4-(2-methylene-1-oxobutyl) phenoxymethyl]-3-methyl-1,2,4- oxadiazole (6r), a novel ethacrynic acid (EA) derivative. The in vitro effect of 6r on cell proliferation of human colon, leukemia, prostate, lung, breast, ovarian and cervical tumor cell lines was assessed using MTT assay and the in vivo effect was determined with an SW620 xenografts nude mice model. The effect of 6r on expressions of GST P1-1 and apoptosis-related proteins were measured by western blotting and the effect on cell apoptosis was analysed by Hoechst 33258 nuclear staining as well as by cell surface staining of annexin V/propidium iodide. The effect on cell cycle was assessed by flow cytometry. Results showed that 6r inhibit proliferation of a range of human cancer cells in vitro and growth of SW620 tumor xenografts in vivo. The anti-proliferative effect of 6r is associated with cell apoptosis as a result of increased ratio of cellular Bax/bcl-2 expression and subsequent cytochrome-c and caspase-3 activation. Unlike EA, 6r did not show any influence on cellular GST P1-1 expression and its anti-proliferative action was associated with cell cycle arrest in G1/S-phase. In conclusion, 6r has the potential to be developed as a chemotherapeutic agent by induction of cell apoptosis but not regulating GST P1-1.     

中药复方参乌胶囊对亨廷顿病大鼠模型运动功能及脑内单胺类神经递质含量的影响

目的：探讨张粒体缺陷在亨廷顿病（HD）中的作用并观察中药复方参乌胶囊的干预作用。方法：雄性SD大鼠分为6组，每组10只。模型组：线粒休呼吸链复合体Ⅱ/Ⅲ抑制剂3－硝基丙酸（3－NPA）20mg/kg隔日腹腔注射1次，共20天；参乌胶囊用药组根据剂量分为小剂量组、中剂量组、大剂量组：从造模前5天开始给予参乌胶囊0．45g/kg、0．9g/kg、1．8g/kg，每日1次，共25天；氟哌啶醇组：造模的同时给予氟哌啶醇，起始剂量为10μg/100g体重，以后隔日递增10μg/100g体重，至100μg/100g体重；正常对照组（9只），隔日腹腔注射与模型组等剂量的生理盐水，蒸馏水灌胃。旷场分析实验检测各组大鼠模型的中枢兴奋状态及空间认知能力，攀网实验检测动物肌力变化，高效液相色谱－电化学检测法分别测定各组动物纹状体中多巴胺（DA）、其代谢产物二羟基苯乙酸（DOPAC）及5－羟色胺（5－HT）的含量。结果：旷场分析实验中模型组大鼠较政党对照组理毛次数、站立次数、跨格次数分别减少74．69％，64．46％，53．06％，具有非常显著性差异（P＜0．01），参乌胶囊用药组较模型组理毛次数增加了68％（P＜0．01）；攀网实验中，各组动物攀附时间无差异；模型组大鼠较正常对照组DA、DOPAC和5－HT的含量明显降低（P＜0．01）；而参乌胶囊用药组、氟哌啶醇组动物纹状体中上述递质及其代谢产物的含量都较模型组明显升高（P＜0．01）。结论：腹腔注射3－NPA可以造成大鼠运动功能及脑纹状体内单胺类神经递质的改变，而中药复方参乌胶囊对3－NPA动物模型的行为学及脑纹状体中单胺类神经递质含量具有明显的改善和提升作用。     

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment

Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.