2，3-吲哚醌抗帕金森病性痴呆作用研究

发布时间：2018-02-13 04:52

本文关键词： ISA 抗PDD Morris水迷宫肌震颤小鼠　出处：《青岛大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的采用经典的东莨菪碱所致的小鼠快速痴呆模型,利用Morris水迷宫设备观察2,3-吲哚醌(2,3-indolinedione,ISA)对痴呆小鼠学习记忆能力的改善作用,并结合槟榔碱单次注射建立小鼠肌肉震颤帕金森病(PD)模型,记录ISA预处理后,小鼠出现震颤的潜伏期和震颤持续时间,证明其抗帕金森病性痴呆(PDD)的作用。方法 1.ISA对痴呆小鼠学习记忆能力的改善作用小鼠随机分成7组,正常对照组(生理盐水10ml·kg-1)、模型组、司来吉兰组(1mg·kg-1)、脑复康组(300mg·kg-1)、ISA小、中、大剂量组(25,50,100mg·kg-1),,灌胃给药连续28天,从第15天开始进行寻找平台训练,第22天用东莨菪碱造模并进行正式水迷宫测试,记录小鼠找到平台的潜伏期和游泳路程,共测试5天。小鼠第27天停止水迷宫实验1天,第28天后撤去平台,记录小鼠穿梭平台的次数,在平台所在象限的游泳路程和游泳时间。 2.ISA对PD模型小鼠肌肉震颤时间及潜伏期的影响小鼠随机分为7组,正常对照组(生理盐水10ml·kg-1)、溶剂组(西黄耆胶混悬液1.25%)、模型组、司来吉兰组(10mg·kg-1)、ISA小、中、大剂量组(25,50,100mg·kg-1),每天灌胃一次,连续14天。于末次灌胃后24小时,除对照组外,其余六个组均给予槟榔碱25mg·kg-1后,每只小鼠从给药至产生肉眼明显可见的肌震颤的时间(震颤潜伏期),以及从肉眼明显可见的肌肉震颤产生至消失所需时间(震颤持续时间),进行统计分析。 3.ISA的急性毒性研究小鼠随机分为5组,每组10只,灌胃给药容积0.5ml/20g体重,观察给药后6d各组动物的死亡和存活情况,计算死亡率和LD50。结果 1.注射东莨菪碱后,模型组小鼠找到平台的潜伏期和上台前游泳路程显著延长(p0.01)。测试5天中,司来吉兰、脑复康和ISA中剂量(50mg·kg-1)均可缩短痴呆小鼠找到平台的潜伏期和上台前游泳路程(p0.05),可有效改善痴呆小鼠的学习能力,三者之间效果无差异；ISA小剂量(25mg·kg-1)和大剂量(100mg·kg-1)组小鼠潜伏期和上台前路程与模型组无差异。 2.平台撤掉后,司来吉兰、脑复康和ISA中剂量(50mg·kg-1)组小鼠站台穿梭次数、站台所在象限游泳路程和站台所在象限游泳时间较模型组有所增加(p0.05),记忆力改善明显,三者之间效果无差异；ISA小剂量(25mg·kg-1)和大剂量(100mg·kg-1)组小鼠站台穿越次数、站台所在象限游泳路程和游泳时间与模型组无差异。 3.槟榔碱能引起小鼠肌震颤(p0.01),说明造模成功；与模型组相比,司来吉兰组的肌震颤持续时间明显缩短(p0.01),ISA25mg·kg-1与50mg·kg-1组的肌震颤持续时间也明显缩短(p0.01)；ISA100mg·kg-1组肌震颤持续时间无改变(p0.05)；与司来吉兰组相比,ISA25mg·kg-1与50mg·kg-1组缩短肌震颤持续时间的疗效无差异(p0.05)。 4.槟榔碱出现明显肌震颤的潜伏期较对照组显著延长(p0.01),说明造模成功；与模型组相比,司来吉兰组的肌震颤潜伏期明显延长(p0.01)；ISA25mg·kg-1的肌震颤潜伏期也有所延长,但无统计学意义(p0.05)；ISA50mg·kg-1与100mg·kg-1组的肌震颤潜伏期无改变(p0.05)。 5.在本试验剂量条件下,ISA对小鼠经口灌胃给药急性半数致死量LDso和95%可信限为：2.0546(1.6574～2.5496)g·kg-1。结论 1.ISA能够改善东莨菪碱所致痴呆小鼠的学习和记忆能力,与临床用药作用效果对比无明显差异。 2.ISA能够缩短槟榔碱引起的小鼠肌震颤时间和潜伏期。 2.ISA具有抗PDD作用,而且天然低毒,结合以往研究结果,作用机制可能与其作用于单胺类神经递质,具有MAOI、抗炎、抗氧化、抗衰老、免疫增强和心血管保护作用等有关。
[Abstract]:objective
The mouse quickly using the classical model of dementia induced by scopolamine, the observation of 2,3- dioxoindoline using Morris water maze devices (2,3-indolinedione, ISA) improving effect on the ability of learning and memory in dementia mice, and combined with a single injection of arecoline in mice muscle tremor of Parkinson's disease (PD) model, ISA records after the pretreatment, the incubation period and the mice showed tremor tremor duration, prove the anti Parkinson's disease dementia (PDD) effect.
Method
Effect of 1.ISA on learning and memory ability of dementia mice
Mice were randomly divided into 7 groups, normal control group (saline 10ml kg-1), the model group, selegiline group (1mg - kg-1), piracetam group (300mg kg-1), ISA, in the large dose group (25,50100mg, kg-1), intragastric administration for 28 days, from fifteenth the day began to find platform training, twenty-second days with scopolamine modeling and formal water maze test, mice swimming time and distance to find the platform, a total of 5 test days. Mice twenty-seventh days to stop water maze for 1 days, twenty-eighth days later removed from the platform, to record the number of mice shuttle platform, in the platform quadrant swimming distance and time.
Effect of 2.ISA on the time and incubation period of muscle tremor in PD model mice
Mice were randomly divided into 7 groups, normal control group (saline 10ml kg-1), solvent group (tragacanthae rubber suspension 1.25%), model group, selegiline group (10mg kg-1), ISA, in the large dose group (25,50100mg - kg-1) by gavage, once a day, continuous in the last 14 days. 24 hours after intragastric administration, except the control group, the other six groups were treated with arecoline 25mg - kg-1, each mouse had apparent visible muscle tremor from administration to time (latency, and tremor) from the naked eye visible muscle tremor generated the required time to disappear (tremors duration), were analyzed.
Study on acute toxicity of 3.ISA
The mice were randomly divided into 5 groups, 10 in each group, and the volume of 0.5ml/20g weight was given to the stomach. The death and survival of the animals in each group of 6D were observed and the mortality and LD50. were calculated.
Result
After the 1. injection of scopolamine, were found in the model group the latency and swimming distance on the front of the stage was significantly prolonged (P0.01). The test in 5 days, selegiline dose, piracetam and ISA (50mg - kg-1) can shorten the incubation period and the dementia mice to find the platform on the stage of swimming distance (P0.05), which can effectively improve the learning abilities, no difference in effect between the three; small dose ISA (25mg - kg-1) and high dose (100mg / kg-1) mice and the latency stage anterior process and model group had no difference.
The 2. platform removed, selegiline, dose of piracetam and ISA (50mg - kg-1) mice platform crossing times, the platform quadrant swimming distance and swimming time in platform quadrant than in the model group increased (P0.05), memory effect was improved obviously, the difference between the three doses of ISA (25mg; kg-1) and high dose (100mg / kg-1) mice platform eross, the platform quadrant swimming distance and swimming time and model group had no difference.
3. mice can cause arecoline muscle tremor (P0.01), indicating that the model was successful; compared with the model group, selegiline group muscle tremor duration shortened significantly (P0.01), duration of ISA25mg - kg-1 and 50mg - kg-1 group amyostasia was significantly shortened (P0.01); ISA100mg group kg-1 muscle tremor duration no change (P0.05); and selegiline group compared to ISA25mg - kg-1 and 50mg - kg-1 group to shorten the duration of the effect of muscle tremor had no difference (P0.05).
4. arecoline appear obvious muscle tremor latency was significantly longer than that of the control group (P0.01), indicating that the model was successful; compared with the model group, selegiline group amyostasia was significantly prolonged (P0.01); ISA25mg kg-1 amyostasia latency has also been extended, but without statistical significance (P0.05); ISA50mg and kg-1 100mg - kg-1 group amyostasia was no change (P0.05).
5. under this test dose, the LDso and 95% confidence limit of ISA for the acute half lethal dose of the oral administration of the mice were 2.0546 (1.6574 ~ 2.5496) g. Kg-1.
conclusion
1.ISA can improve the learning and memory ability of scopolamine induced dementia mice, and there is no significant difference compared with the effect of clinical medication.
2.ISA can shorten the time of arecoline induced muscle tremors and latency.
2.ISA has anti PDD effect and low toxicity. Combined with previous studies, the mechanism may be related to its role in monoamine neurotransmitters, MAOI, anti-inflammatory, anti-oxidation, anti-aging, immune enhancement and cardiovascular protection.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.16

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