人参再造丸对帕金森病鼠模型旋转行为的影响

目的 观察人参再造丸对帕金森病(PD)鼠模型的旋转行为的影响。方法 将6-羟基多巴胺用立体定向法注入大鼠一侧中脑被盖腹侧区制作PD大鼠模型，并分为对照组、美多巴组、人参再造丸组、人参再造丸与美多巴联合组4组，由阿朴吗啡诱发PD鼠旋转行为，观察各组15d、1月、2月、3月旋转圈数，2个月时启动时间、最高转速及持续时间等。结果 人参再造丸组旋转圈数随时间延长下降明显，2个月时行为学改善尤为显著；人参再造丸联合小剂量美多巴组15d旋转圈数即有下降，并随时间延长下降显著。结论 人参再造丸联合小剂量美多巴治疗PD，不仅起效迅速，且疗效持久，不良反应小。     

不同剂量左旋多巴对帕金森病大鼠行为学影响

目的观察不同剂量左旋多巴治疗帕金森病（PD）的效果,并进一步探讨合理使用左旋多巴治疗PD的剂量。方法采用6-OHDA脑立体定向注射术建立大鼠PD模型,采用行为学观察法观察3种不同剂量左旋多巴[按体重10、50、100mg/（kg.d）]作用不同时间（1、3、5、7d）对PD大鼠黑质细胞毒性作用后的行为学变化以及停止左旋多巴治疗后7d各项指标的变化。结果与对照组比较,小剂量组大鼠旋转圈数随左旋多巴使用剂量和时间增加而减少,中、大剂量组大鼠旋转圈数随左旋多巴使用剂量和时间增加而增加;各组大鼠旋转启动时间随左旋多巴使用剂量和时间增加而减少,最高转速及持续时间则随使用剂量增加而增加。结论应尽可能以小剂量、间隔使用左旋多巴治疗PD。     

帕金森病大鼠模型的实验研究

目的 观察帕金森病（PD）大鼠模型行为学变化特点。方法 通过改良PD大鼠模型，观察30只大鼠模型成功后1、7、14天旋转行为的多项指标变化，如：启动时间、持续时间、最高转速、旋转圈数等。结果 1－14天时PD大鼠启动时间逐渐延长、持续时间逐渐缩短，最高转速与旋转圈数不变。结论 改良PD大鼠模型制作方法科学、简单、定位可靠；PD大鼠最高旋转速度、旋转圈数能反映黑质损伤程度。     

不同剂量左旋多巴对帕金森病大鼠行为学影响实验研究

目的　观察不同剂量左旋多巴 (L - dopa)治疗帕金森病 (PD)的效果 ,探讨 L - dopa治疗帕金森病的合理方法。方法　通过 6- OHDA脑立体定向注射术建立大鼠 PD模型 ,采用行为学、TUNEL、原位杂交的方法观察左旋多巴小、中、大 3种不同剂量 [10 mg/(kg· d)、5 0 mg/(kg· d)、10 0 mg/(kg· d) ]、不同的作用时间 (1d、3 d、5 d、7d)对 PD大鼠黑质细胞的毒性作用 ,并观察治疗后 7天各项指标的变化。结果　与对照组比较 ,小剂量组大鼠旋转圈数随 L- dopa使用计量和时间增加而减少 ,中、大剂量组相反 ,旋转启动时间随 L- dopa使用剂量和时间增加而加速 ,最高转速及持续时间则相反。结论　我们应尽可能小剂量、间隔使用 L - dopa治疗 PD。     

恩他卡朋对帕金森病大鼠的疗效

目的:观察恩他卡朋与左旋多巴/苄丝肼(美多芭)联用对帕金森病大鼠的治疗作用。方法:6-羟多巴(6-OHDA)毁损内侧前脑束(MFB)建立SD大鼠PD模型。成模大鼠腹腔注射不同剂量的美多芭与恩他卡朋,观测大鼠旋转圈数和持续时间。结果:单用恩他卡朋不能诱导PD大鼠旋转。采用美多芭(6.25、12.5mg·kg-1)和不同剂量的恩他卡朋(10、5、0mg·kg-1)联用的PD大鼠,旋转圈数明显增加、旋转时间也明显延长;恩他卡朋的剂量越大,旋转运动的持续时间越长,但出现旋转反应高峰的时间向后推迟。结论:足量的恩他卡朋可以加强左旋多巴的疗效,半量的恩他卡朋疗效欠佳。     

帕金森病行为学和黑质形态学实验研究

目的观察帕金森病大鼠行为学及其形态学特点。方法本试验通过PD大鼠模型,采用行为学观察、TUNEL法、HE染色、Nissl染色及电镜方法,观察模型成功后1d、7d、14d PD大鼠行为、形态学变化。结果 PD大鼠旋转圈数无明显变化,凋亡细胞、尼氏细胞逐渐减少,超微结构损伤逐渐加重。结论 PD大鼠旋转行为变化有其病理学基础。     

镁对帕金森病大鼠黑质多巴胺神经元的影响

目的观察镁对帕金森病(PD)大鼠黑质多巴胺神经元影响及其作用机制。方法应用6-羟基多巴胺(6-OHDA)制备偏侧PD大鼠模型后分为硫酸镁组、美多巴组、混合组(硫酸镁+美多巴)和对照组(生理盐水),并给予相应药物灌胃治疗28d。观察治疗后各组大鼠旋转行为的变化;免疫组化法检测黑质酪氨酸羟化酶(TH)阳性神经元数量;生化法测定损毁侧纹状体超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;逆转录聚合酶链反应检测损毁侧黑质caspase-3 mRNA表达;Western Blot法检测核因子(NF)-кBP65水平。结果治疗后仅混合组出现较稳定的向对侧的旋转行为;TH阳性神经元数混合组较其他各组明显增加(均P<0.05);与对照组和美多巴组比较,硫酸镁组和混合组SOD、GSH-Px活性显著增高,MDA、caspase-3 mRNA、NF-кBP65水平显著降低(均P<0.05);硫酸镁组与混合组间差异无统计学意义。结论镁及美多巴联合治疗可提高PD模型脑内多巴胺神经元存活、降低氧化应激损伤、减少神经元凋亡,改善PD大鼠症状。     

不同剂量左旋多巴对帕金森病运动并发症大鼠模型行为学的影响

目的：比较不同剂量左旋多巴长期注射对帕金森病（PD）运动并发症大鼠模型异常不自主运动（AIM）和疗效减退的影响,以确定合适的左旋多巴用药剂量和行为学评价标准。方法：立体定向SD大鼠右侧前脑内侧束,注射6羟基多巴建立PD大鼠模型。成模PD大鼠随机分为3组,分别腹腔注射左旋多巴酯：小剂量组（20mg·kg（-1）·d（-1））、中剂量组（50mg·kg（-1）·d（-1））和大剂量组（100mg·kg（-1）·d（-1））,每天2次,持续21d。比较3组PD大鼠模型AIM各组份的评分情况及对侧旋转反应时间。结果：左旋多巴3种剂量均可诱发PD大鼠出现相似程度的口面、前肢、轴向AIM,但大剂量组大鼠旋转AIM的评分高于小剂量组（P〈0.05）,且旋转反应时间缩短幅度大于中剂量组和小剂量组（P〈0.05）。结论：小剂量左旋多巴就可诱发PD大鼠出现明显的AIM,又能避免过于剧烈的旋转运动对AIM评分的干扰;但观察疗效减退现象需要选用大剂量左旋多巴以诱导出稳定下降的旋转反应时间。     

普拉克索添加治疗帕金森病临床随机对照研究

目的 评价新型多巴胺受体激动剂普拉克索联合美多巴与单用美多巴治疗帕金森病(PD)患者的疗效及安全性. 方法 采用随机对照开放式研究,将70例PD患者按照随机数字表法分为普拉克索+美多巴组和美多巴组,每组各35例.治疗12周后判断其疗效及安全性.疗效判定的主要指标为统一PD评定量表第Ⅲ部分(UPDRSⅢ)的运动检查总评分相对患者基线的变化和第Ⅱ部分(UPDRS Ⅱ)的日常生活活动能力总评分相对患者基线的变化;次要指标为第Ⅰ部分(UPDRS Ⅰ)的精神、行为和情感总评分相对患者基线的变化和第Ⅳ部分(UPDRS Ⅳ)的治疗并发症总评分相对患者基线的变化和美多巴药物每日剂量相对基线的变化.安全性指标依据药物的不良反应来判定. 结果 普拉克索+美多巴组患者UPDRS Ⅲ总评分均值与基线相比下降了11.40分,高于美多巴组(9.26分),比较差异有统计学意义(P<0.05);UPDRS Ⅱ总评分均值与基线相比下降了4.57分,高于美多巴组(4.50分),比较差异无统计学意义(P<0.05);UPDRS Ⅰ总评分均值与基线相比下降了0.66分,低于美多巴组(1.14分),差异无统计学意义(P0.05);UPDRS Ⅳ总评分均值与基线相比下降了0.22分,美多巴组则升高了0.06分,差异有统计学意义(P<0.05).与基线相比,治疗后12周普拉克索+美多巴组美多巴的日用量下降了163.57 mg/d,美多巴组升高了8.57 mg/d,差异有统计学意义(P<0.05).普拉克索+美多巴组在治疗后12周发生疗效减退、症状波动、异动症的例数均低于美多巴组,差异有统计学意义(P<0.05).美多巴组出现了明显的疗效减退、症状波动、异动症,而普拉克索+美多巴组无明显的上述症状,但有2例出现突然入睡发作、1例嗜睡、1例直立性低血压. 结论 普拉克索+美多巴组在改善PD运动功能方面优于美多巴组,在日常活动,精神、行为和情绪方面疗效相似.同时服用普拉克索可以明显减少美多巴的用量及其治疗后所引起的并发症(疗效减退、症状波动及异动症)的发生率.普拉克索可引起突然入睡发作、嗜睡、直立性低血压等副作用.     

银杏叶提取物治疗帕金森病大鼠的研究

目的　观察银杏叶提取物 (EGb)治疗帕金森病 (PD)的效果 ,论证EGb治疗PD的可能性。方法　通过PD大鼠模型 ,采用免疫组织化学、HE染色、电镜及旋转行为检查的方法 ,观察模型成功后EGb(EGb组 )治疗 1天、7天、14天大鼠旋转行为及黑质病理变化 ,并与对照组 (PD组 )比较。结果　EGb组酪氨酸羟化酶染色显著高于PD组 (P <0 0 5 ) ,旋转圈数、黑质bFGF蛋白表达均较PD组减少 (均P <0 0 5 ) ,EGb组黑质超微结构及HE染色结构损伤均减轻。结论　银杏叶提取物可能是治疗PD的有效药物     

蛋白酶体抑制剂诱导多巴胺能神经元变性及诱导型一氧化氮合酶变化

目的探讨蛋白酶体（proteasome）功能下降在帕金森病（PD）发病机制中的作用，以及模型大鼠脑内黑质部位诱导型一氧化氮合酶（iNOS）是否参与蛋白酶体抑制剂Lactacystin诱导的多巴胺能神经元变性。方法将30只健康雄性SD大鼠分为5组（生理盐水对照组，1d组、3d组、1周组、3周组），每组6只。将蛋白酶体抑制剂Lactacystin立体定向注射至大鼠黑质部位，记录大鼠在不同时间点的行为学改变，并用免疫组化方法观察生理盐水对照组及不同时间点组（1d、3d，1周、3周）大鼠黑质区多巴胺能神经元变性及iNOS变化。结果Lactacystin注射1周后大鼠开始出现自发性活动减少，阿朴吗啡可诱导出旋转行为；3周后，30min旋转次数为258．90±11．56；实验3周组黑质部位TH阳性细胞减少。1d后iNOS阳性细胞明显增多，3d时达高峰，1周后开始下降，3周时基本消失。结论蛋白酶体功能下降可能是多巴胺能神经元变性的始动因素，而iNOS上调可能是多巴胺能神经元变性的重要过程。     

Progressive ventricular enlargement in the absence of high ventricular pressure in an experimental neonatal rat model

OBJECT: In the present study, we compared ventricular pressures (VP) and the progression of ventricular enlargement in a new experimental neonatal hydrocephalus model, to gain an understanding of how communicating hydrocephalus progresses. METHODS: Kaolin was injected into the subarachnoid space at the cranial convexity of neonatal rats. Gross examination was performed on the 3rd, 5th and 7th days, and ultrasonographic examination on the 15th day, and at the end of the 1st and 2nd months following the kaolin application. Ventricular size indexes (VSI) were calculated in the case of a large ventricular dilatation. VPs were assessed on the 15th day, and at the end of the 1st and 2nd months, with a computerized data acquisition system. CONCLUSIONS: In the 1st and 2nd months VSIs were significantly higher than in control rats on the 15th day after kaolin administration. VP on the 15th day was significantly increased compared with that in control rats. VP in the 1st month was still high, but had subsided. In the 2nd month VP was not increased over control. In the late stages, the progression of infantile communicating hydrocephalus is not related to VP levels.     

美多巴单用及联合二氢麦角隐亭治疗帕金森病的临床疗效

目的 探讨兰美多巴单用及联合二氢麦角隐亭治疗帕金森病的临床疗效.方法 选择我院收治的中晚期帕金森病患者94例,随机分为观察组和对照组,2组均给予美多巴进行治疗,观察组联合给予二氢麦角隐亭治疗,比较2组临床治疗效果.结果 观察组总有效率为74.47%,对照组总有效率为46.81%,2组治疗效果比较经统计学分析比较,差异有统计学意义（P＜0.05）.2组治疗后帕金森氏病综合评分均较治疗前降低,观察组较对照组明显,经统计学分析比较,差异有统计学意义（P＜0.05）.2组不良反应发生情况比较,差异无统计学意义（P＞0.05）.结论 美多巴联合二氢麦角隐亭治疗中、晚期帕金森病疗效满意且安全,值得临床推广使用.     

血清同型半胱氨酸水平与帕金森病的关系

目的探讨帕金森病(PD)患者伴发高同型半胱氨酸血症(HHcy)情况及美多巴对其血清同型半胱氨酸(Hcy)水平的影响。方法选择2006-06-01-2009-12-31入住作者医院的PD患者53例,按入院前是否服用美多巴治疗分为非美多巴组和美多巴组,两组患者入院后均予美多巴口服治疗;另选择31名同期健康体检者为对照。采用荧光偏振免疫分析法(FPIA)检测血清Hcy水平,微粒子酶免分析法(MEIA)检测血清叶酸(FA)及维生素B12(VitB12)水平。收集患者初次就诊及初次复诊时的血清Hcy、FA、VitB12水平资料至2010-01-30,并进行分析比较。结果 (1)初次就诊时非美多巴组和美多巴组PD患者血清Hcy水平〔分别(17.28±6.79)、(18.50±6.56)μmol/L〕均高于健康对照组〔(13.49±3.21)μmol/L〕(均P<0.01),HHcy的比例〔分别为50%(14/28)和76%(19/25)〕亦高于健康对照组〔29%(9/31)〕(均P<0.01),而血清FA、VitB12的水平无统计学差异(均P>0.05)。HHcy患者的血清Hcy水平与FA、VitB12水平无相关性(分别r=0.118,P=0.455;r=0.001,P=0.995)。(2)非美多巴组患者复诊时血清Hcy水平〔(15.84±3.33)μmol/L〕较治疗前〔(12.92±3.15)μmol/L〕升高(P<0.05),血清FA、VitB12水平同治疗前比较无统计学差异(P>0.05)。美多巴组患者服用美多巴治疗后血清Hcy、FA、VitB12水平同初次就诊时比较均无统计学差异(均P>0.05)。结论服用美多巴可能使PD患者血清Hcy水平升高,但可能不是PD患者伴有HHcy的惟一原因。     

Long-Term Changes in Behavior and the Content of BDNF in the Rat Brain Caused by Neonatal Isolation: The Effects of an Analog of ACTH(4-10) Semax

Exposure to stress during early postnatal development can cause neurological disorders in adulthood. The aim of this study was to evaluate changes in behavior, learning ability, and the content of the neurotrophic factor BDNF in rats that underwent neonatal stress. In addition, we studied the possibility of correction of the effects of neonatal stress by subsequent administration of an analog of the ACTH(4-10) fragment Semax. Neonatal isolation (NI) was used as a stress stimulus. Rat pups were separated from their mother and littermates for 5 h per day each day during the period from the 1st to the 14th day of life. The control animals were left in their nest in the first 2 weeks of life. From the 15th to 28th day of life, half of the rats subjected to NI were intranasally treated with Semax daily at a dose of 0.05 mg/kg. The remaining animals received intranasal injection of solvent at the same time. It has been shown that NI leads to an increase in the level of anxiety, a slight increase in depression, and impaired retention of the passive avoidance task in rats during the second month of life. At the age of 1 month, we observed an increase in the content of BDNF in the frontal cortex in the rats with NI; at the age of 2 months, a decrease occurred in the neurotrophin level in the hippocampus. Administration of Semax to rats subjected to NI decreased anxiety and depression, improved learning ability, and normalized the BDNF content in brain structures of animals. Therefore, chronic intranasal Semax administration after NI weakens the negative effects of neonatal stress.     

高压氧对脑白质疏松大鼠的神经保护作用

目的探讨高压氧对脑白质疏松大鼠的行为学、海马结构及神经元影响。方法采用双侧颈总动脉结扎法制作缺血缺氧脑白质疏松模型,术后2 w脑白质疏松形成。第15天起给予2.0ATA的压力治疗1 h/d,共14 d。定位航行实验、足迹实验观察大鼠行为学变化,HE染色观察大鼠神经元形态学变化,TUNEL法观察凋亡神经元情况。结果与假手术组相比,手术组及高压氧治疗组大鼠认知功能明显减弱,神经元数量减少,排列疏松,胞核固缩,TUNEL阳性细胞增多;与手术组比较,高压氧组认知功能有所改善,神经元数量多且排列整齐。TUNEL法测高压氧组神经元凋亡情况改善。结论高压氧可改善脑白质疏松大鼠海马结构和神经元凋亡情况,且有助于其认知功能的恢复。     

Effects of cerebellectomy at day 15 on the ontogenesis of the equilibrium behavior in the rat

Young cerebellectomized and control (sham-operated) DA/HAN strained rats, 1 day to 1 month old, were submitted to an equilibrium test consisting for the animals in maintaining their equilibrium when placed on a horizontal mast rotating around its longitudinal axis at 10 or 20 rpm (slow and fast rotation rates, respectively). Cerebellectomized animals, operated when 15 days old, were either naive (tested at one given day) or trained; these last ones were trained before and after the operation, or only before, or only after, according to a slow or a fast rotation rate. Control rats were also either naive or trained in conditions similar to those given to operated animals. Relevant comparisons show that: (1) rats cerebellectomized at day 15 which have not been trained before the operation are unable to learn a given motor pattern. (2) When trained before the operation, the animals learn the motor patterns that they use to maintain their equilibrium upon the rotating mast as well as controls. (3) Postoperative training is inefficient in the acquisition of the equilibrium behavior whether the animals were trained preoperatively or not. (4) Compared to the slow rotation rate (10 rpm), the evolution of the equilibrium behavior in cerebellectomized rats is not altered when the rotation rate is increased to 20 rpm, that is when the task is more difficult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.     

Nocturnal rotation in normal rats: Correlation with amphetamine-induced rotation and effects of nigro-striatal lesions

Normal unoperated rats were observed to rotate (turn in circles) at night. For most (91.7%) rats, the preferred direction of rotation was consistent across hours and days and was the same as the direction of rotation elicited by D-amphetamine (1.0 mg/kg) during the day. The magnitudes of nocturnal and D-amphetamine-induced rotation were also highly correlated. After rats showed stable diurnal patterns of rotation, unilateral lesions were made in either the substantia nigra, the nigrostriatal bundle or the caudate nucleus. All lesions produced transient contralateral rotation within the first 24-48 h after surgery. The time-course of this contralateral rotation was more prolonged after nigral lesions than after nigrostriatal bundle lesions and least after caudate lesions, suggesting that the duration of a degeneration release of dopamine is proportional to the length of the degenerating axon. Lesion size was correlated with the intensity of contralateral rotation but not with the time-course. At each rostralcaudal level, the magnitude of contralateral rotation was greater if the lesion was in the side of the brain opposite to the preoperative direction of rotation than if in the same side. By three days after surgery, all rats returned to a mostly normal diurnal cycle with the direction of rotation now being ipsilateral to the lesion. D-Amphetamine potentiated the ipsilateral rotation, though rats with lesions in the same side of the brain as the preoperative direction of rotation had larger drug responses than rats with similar lesions in the opposite side of the brain. By one month after surgery, the direction of spontaneous rotation of most rats had returned to the preoperative direction. As at all other times, the magnitude of rotation was, in part, dependent on the side of the lesion with respect to the preoperative bias. It is suggested that, following a unilateral lesion, compensatory processes occur to a greater extent if the lesion is in the normally more active side of the brain.     

美多芭联合恩他卡朋治疗对帕金森病患者血浆同型半胱氨酸水平的影响

目的探讨美多芭联合恩他卡朋治疗对帕金森病(PD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法选取30名健康体检者作为对照组,20例未服用过左旋多巴(LD)制剂的PD患者为未服药组,63例美多芭治疗的PD患者为美多芭组,49例美多芭联合恩他卡朋治疗的PD患者为联合组。检测患者外周血中的LD稳态峰浓度并进行统一PD评分量表Ⅲ(UPDRSⅢ)的评分。检测所有研究对象的血浆Hcy水平。结果联合组患者LD血浆浓度明显高于美多芭组(P0.05)。美多芭组及联合组患者UPDRSⅢ评分均明显低于未服药组(均P0.05)。与对照组比较,未服药组、美多芭组及联合组患者血浆Hcy水平均明显升高(均P0.05);且美多芭组患者血浆Hcy水平明显高于未服药组及联合组(均P0.05)。结论美多芭联合恩他卡朋能显著降低PD患者血浆Hcy水平,对PD治疗有积极意义。