农药百草枯致小鼠帕金森病模型研究

目的:研究百草枯致C57BL小鼠帕金森病模型中脑黑质多巴胺能神经元的损伤和纹状体多巴胺递质的变化。方法:C57BL小鼠每周两次百草枯(10mg·kg-1体重)腹腔注射,共6周。悬挂法观察小鼠行为学改变。中脑黑质部位行酪氨酸羟化酶(TH)免疫组化染色检查黑质部多巴胺能神经元变化。HPLC法观测纹状体中多巴胺含量的变化。结果:百草枯组C57BL小鼠出现显著的行为学障碍,悬挂得分减少;中脑黑质细胞数量减少;纹状体多巴胺含量降低。结论:C57BL小鼠慢性暴露于百草枯可成功复制帕金森病模型。     

百草枯所致帕金森病小鼠黑质纹状体通路多巴胺转运体减少

目的 :探讨多巴胺转运体 (dopaminetransporter ,DAT)是否参与百草枯所致PD的发病机制。方法 :用口服百草枯的途径 ,建立小鼠帕金森病模型 ;应用免疫组织化学和原位杂交方法分别观察小鼠纹状体区DAT的水平和黑质部基因表达的变化。结果 :每天口服百草枯 10mg·kg-1的C5 7BL/6小鼠 ,2个月后自发性活动明显减少。纹状体区的DAT含量较口服盐水对照组减少 42 % (P <0 0 1) ,黑质部DATmRNA的表达降低 3 7 2 % (P <0 0 1)。结论 :百草枯可造成小鼠帕金森病样的行为表现。黑质纹状体通路DAT含量和基因表达的降低 ,提示DAT参与了百草枯所致的帕金森病发病机制     

百草枯对小鼠黑质纹状体通路囊泡单胺转运体2的影响

目的 :探讨囊泡单胺转运体 2 (vesicularmonoaminetransporter 2 ,VMAT2 )是否参与百草枯所致帕金森病 (Parkinson’sdisease ,PD)的发病机制。方法 :用口服百草枯的途径 ,建立小鼠PD模型 ;应用免疫组织化学和原位杂交法分别观察小鼠纹状体区VMAT2的水平和黑质部基因表达的变化。结果 :每天口服百草枯 10mg·kg-1的C5 7BL/ 6小鼠 ,2个月后自发性活动明显减少。纹状体区的VMAT2含量较口服盐水对照组减少 5 1 7% (P <0 0 1) ,黑质部VMAT2mRNA的表达降低 5 2 7% (P <0 0 1)。结论 :百草枯可造成小鼠PD样的行为表现 :黑质纹状体通路VMAT2含量和基因表达的降低 ,提示VMAT2参与了百草枯所致的PD发病机制。     

去铁胺对百草枯处理小鼠脑内多巴胺含量和氧化应激的影响

目的:探讨铁螯合剂去铁胺对百草枯干预小鼠脑内多巴胺(DA)含量和氧化应激的影响。方法:C57BL/6小鼠随机分为百草枯组、去铁胺干预组和正常对照组,高效液相色谱分析(HPLC)测定纹状体DA含量,化学比色法分别测定中脑黑质部位超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶活性(GSH-Px),以及丙二醛(MDA)含量的变化。结果:腹腔注射百草枯20mg·kg-1·d-1连续3d后,小鼠自发性活动明显减少,纹状体DA含量明显减少,黑质部SOD和GSH-Px的活性明显下降,MDA含量明显升高,与正常对照组比差异有统计学意义(P<0.05);给予去铁胺干预后小鼠纹状体DA含量和黑质部SOD和GSH-Px的活性明显增加,MDA含量明显降低,与百草枯组比差异有统计学意义(P<0.05)。结论:去铁胺干预后使小鼠纹状体的DA含量升高,氧化应激程度减轻。提示去铁胺对小鼠黑质纹状体通路DA能神经元可能具有一定的保护作用。     

粒细胞集落刺激因子对百草枯干预小鼠黑质纹状体通路的影响

目的探讨粒细胞集落刺激因子(G-CSF)对百草枯干预小鼠脑内黑质纹状体通路的影响。方法 C57BL/6小鼠随机分为百草枯组、G-CSF干预组和对照组(均n=8)。高效液相色谱分析测定纹状体多巴胺含量,同时采用免疫组化ABC法观察黑质部酪氨酸羟化酶(TH)阳性表达神经元。结果腹腔注射百草枯20 mg·kg~(-1)·d~(-1),连续5 d后,小鼠自发性活动明显减少,纹状体多巴胺含量明显减少,黑质部TH阳性表达明显减少,与对照组比较差异有统计学意义(P0.05);给予G-CSF干预后纹状体多巴胺含量和黑质部TH阳性表达明显增加,与百草枯组比较差异有统计学意义(P0.05)。结论 G-CSF干预后小鼠纹状体的多巴胺含量升高,黑质部TH阳性表达增加,提示G-CSF对小鼠黑质纹状体通路多巴胺能神经元可能具有一定的保护作用。     

小鼠慢性暴露于百草枯对其脑线粒体呼吸链复合酶活性的影响

目的 :探讨百草枯对黑质细胞线粒体呼吸链的影响和导致黑质细胞损害的可能机制。方法 :测定通过口服途径亚慢性暴露于百草枯、MPTP或等量生理盐水的小鼠脑内线粒体呼吸链中复合酶Ⅰ、Ⅱ、Ⅳ及柠檬酸合成酶的活性。结果 :百草枯和MPTP干预组小鼠黑质部及纹状体线粒体呼吸链中复合酶Ⅰ的活性显著降低 ,额叶和小脑中该酶的活性无变化。各组小鼠黑质部、纹状体、额叶及小脑中复合酶Ⅱ、Ⅳ及柠檬酸合成酶的活性均无显著差异。结论 :百草枯透过血脑屏障后选择性地导致黑质部和纹状体中线粒体功能障碍。     

百草枯和硫丹对C57BL小鼠脑内多巴胺能与乙酰胆碱能损害的比较

目的 :研究百草枯 (PQ)、硫丹 (ES)对C5 7BL小鼠脑内多巴胺 (DA)能与乙酰胆碱 (ACh)能损害的比较。方法 :给小鼠喂食PQ、MPTP、ES ,观其行为变化 ,并结合放射自显影测小鼠大脑皮质各区、纹状体、海马、丘脑区ACh受体 (AChR)及纹状体区DA转运体(DAT)和DAD2 受体 (DAD2 R)量。结果 :PQ、ES和MPTP组小鼠脑内AChR量与对照组相比无明显差异 ,而纹状体DAT和DAD2 R量均显著下降。结论 :PQ和ES主要损害的是小鼠脑内的DA能系统 ,而对ACh能系统影响不大。     

百草枯致小鼠黑质部多巴胺能神经细胞凋亡的作用

目的:探讨百草枯致小鼠黑质细胞死亡的方式及神经毒性机制。方法:C57BL小鼠口服百草枯不同时间后采用酪氨酸羟化酶(TH)免疫组化及TUNEL法、流式细胞仪、透射电镜检测黑质部多巴胺能神经元的凋亡现象。结果:TH免疫组化及TUNEL双标染色检查示C57BL小鼠暴露于百草枯后2周后黑质部多巴胺能神经细胞即有凋亡样改变,流式细胞仪检测显示小鼠于暴露百草枯1个月时凋亡细胞数最多,与对照组相比,P<0.001;2个月时有所减少,但仍多于对照组(P<0.01)。结论:小鼠暴露于百草枯一定时间后可引起黑质部多巴胺能神经元发生凋亡,这可能是百草枯的神经毒性作用机制之一。     

司来吉兰对帕金森病小鼠黑质的神经保护作用及其评价

目的:探讨司来吉兰对PD小鼠黑质的神经保护作用并对其进行评价。方法:24只雄性C57BL小鼠被随机分成三组,即司来吉兰预处理组、模型组和对照组。分别给予司来吉兰+MPTP、MPTP和生理盐水,连续应用7天。取黑质分别行流式细胞学检查,分别测定黑质细胞凋亡率、bcl-2和bax蛋白表达的平均荧光强度以及黑质酪氨酸羟化酶(TH)免疫组化和透射电镜观察。21只雄性C57BL小鼠被随机分成司来吉兰预处理组、模型组和对照组。处理方法同前。7天后应用多巴胺转运蛋白(DAT)显像剂99Tcm-TRODAT-1对每组的纹状体DAT功能保留情况进行评价。结果:模型组黑质凋亡率高于司来吉兰预处理组和对照组(P<0.01,P<0.01),司来吉兰预处理组与对照组的凋亡率无差异(P>0.05)。与对照组比较,模型组bax高表达(P<0.01)而bcl-2低表达(P<0.01):与对照组比较,司来吉兰预处理组bax低表达(P<0.01)而bcl-2高表达(P<0.01)。司来吉兰预处理组和对照组小鼠的纹状体DAT功能无差异(P>0.05)。与对照组和司来吉兰组比较,模型组小鼠纹状体DAT功能明显降低(P<0.01,P<0.01)。结论:司来吉兰预处理对小鼠黑质产生神经保护作用。司来吉兰对MPTP处理小鼠黑质的保护作用机制之一是通过上调bcl-2基因和下调bax基因而实现的:新型DAT显像剂一99Tcm-TRODAT-1可用于PD的神经     

丁基苯酞对帕金森模型小鼠中脑黑质多巴胺能神经元数及TH、TNF-α蛋白表达的影响

目的研究丁基苯酞(dl-3n-butylphthalide,NBP)对由MPTP诱导的C57BL/6小鼠帕金森模型中脑黑质多巴胺能神经元数及TH、TNF-α蛋白表达的影响,进一步探讨其保护机制。方法 24只C57BL/6小鼠,随机分成3组:正常对照组,MPTP组,NBP治疗组。MPTP腹腔注射法制备帕金森模型,免疫组织化学法观察中脑黑质TH阳性神经元细胞数,蛋白质印迹法观察中脑黑质TH、TNF-α蛋白含量的变化。结果 (1)与正常对照组比较,MPTP组可见帕金森病小鼠中脑黑质TH阳性神经元明显减少(P0.01);与MPTP组比较,NBP治疗组帕金森病小鼠中脑黑质TH阳性神经元数目明显增加(P0.01);(2)与正常对照组比较,MPTP组帕金森病模型小鼠中脑黑质TH蛋白表达减少(P0.01),而TNF-α蛋白表达增加(P0.05);(3)与MPTP组比较,NBP治疗组帕金森病模型小鼠中脑黑质TH蛋白表达明显增加(P0.01),而TNF-α蛋白表达减少(P0.05)。结论丁基苯酞可能通过提高中脑黑质中TH的含量及减少TNF-α炎性介质表达发挥对MPTP所致C57BL/6小鼠帕金森模型的神经元保护作用。     

Resistance to alternatives to hospitalization

Hospitalization has endured as the predominant form of psychiatric treatment for serious mental illness, despite accumulated evidence that outpatient treatment, ranging from halfway houses to day programs to traditional clinics, is equal or superior to inpatient treatment. Reasons for the apparent reluctance to use alternatives to the hospital include social prejudice against community treatment, economic disincentives, administrative chaos, training, professional sociology, and the countertransference meanings of hospitalization. The foregoing is not an argument against hospitalization, but rather an argument for being very clear about policy objectives and treatment goals. If these objectives and goals are made explicit, proposals can be evaluated for their efficacy. If community tenure, the assumption of responsibility for him or herself, and relinquishment of the patient role are goals, then hospitalization must be examined more skeptically. For society, this means the assumption of more responsibility for the establishment of a system of mental health care, for enunciating national policy goals and implementing them consistently, and for committing the necessary funds and manpower to this endeavor. For the clinician, it means examining the clinical efficacy of his or her treatment recommendations and distinguishing between responsibility for the patient's treatment and responsibility for the patient's life. The abdication of social responsibility for the patient and the assumption of omnipotent clinical responsibility for him or her lead inexorably to more institutional and more restrictive treatment, even in the absence of evidence that such measures are therapeutically effective.     

Competency to Consent to Treatment

Competency to consent to treatment is an especially critical determination to make in the field of psychiatry. Psychiatric patients are often capable, despite their illness, of self-advocacy. Careful assessments are required to differentiate competent patients from incompetent patients. Moreover, the character of their illness, from psychosis to organic brain disease, has been found to correlate with a lack of competency. The presence of auditory hallucinations or delusions, however, are not pathognomonic of incompetency. Currently, there exists no standardized method to establish competency, either in psychiatric or in medical patients. This is a review of the several instruments developed by various researchers attempting to create one. It finds promise in several questionnaires that have good inter-rater reliability and validity.