百可利对氧化震颤素致小鼠震颤的抑制作用及其机制研究

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目的:探讨百可利对氧化震颤素致小鼠肌肉震颤的抗震颤效果及其作用机制.方法:将KM小鼠随机分为正常对照组、模型组、百可利给药组(120,240和480 mg·kg-1)、阳性药山莨菪碱组(10 mg· kg-1)和美多芭组(50 mg·kg-1),百可利各给药组和阳性药组灌胃(ig)给药,qd,共28 d.正常组和模型组(ig)给予等剂量的生理盐水.采用腹腔注射(ip)氧化震颤素制备小鼠肌肉震颤的急性模型;测定小鼠肌肉震颤的潜伏期、持续时间和震颤频率,评价小鼠的震颤行为,测定小鼠的流涎分泌量探讨震颤与外周神经作用的相关性;采用生化试剂盒测定谷胱甘肽过氧化物酶(GSH-PX),乙酰胆碱酯酶(AChE),胆碱乙酰转移酶(ChAT)的活性和丙二醛(MDA)的含量;采用高效液相电化学法(HPLC-ECD)测定脑组织内单胺类神经递质的水平变化.结果:模型组动物出现明显的震颤、流涎以及体毛竖起等症状,与模型组相比,ig给予各剂量的百可利1 d未见明显抑制作用.连续给药7,14,21和28 d后,百可利可明显延长震颤小鼠的潜伏期、缩短持续时间和降低震颤频率,显著降低乙酰胆碱水平,恢复模型组动物脑内DOPAC,DA神经递质的改变,调节了脑内乙酰胆碱和多巴胺的动态平衡.结论:百可利长期给药能明显改善小鼠的震颤行为,其机制可能与调节脑内神经递质有关.“,”Objective: To investigate the antitremor effect and mechanism of baicalein on oxotremorineinduced muscle tremor in mice. Methods: KM mice were randomly divided into normal control group, model group, baicalein (120, 240 and 480 mg·kg-1)group, anisodamine group (10 mg·kg-1)and madopar (50 mg·kg-1)group. The administration group and the positive drug group were administered with drugs once a day for 28 d. Normal and model groups were given equal doses of saline. The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine, and the latency, duration and frequency of muscle tremor in mice were measured immediately. The saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function. The activity of glutathione peroxidase (GSH-PX), acetyl cholinesterase (AChE), choline acetyltransferase (ChAT)and the content of malondialdehyde (MDA)were determined by biochemical kit. The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD). Results: The animals in the model group developed obvious tremoring,salivating and erecting and other symptoms. Compared to the model group,none of the baicalein groups had obvious inhibitory effect. After 7,14,21 and 28 d of continuous administration,baicalein could significantly prolong the latency of tremor,shorten the duration and reduce the tremor frequency,significantly decrease the levels of acetylcholine, and recover the changes of DOPAC and DA neurotransmitters in the brain of model group,which regulated the dynamic balance of acetylcholine and dopamine in the brain. Conclusion: Long-term administration of baicalein can improve the tremor behavior of mice,and the mechanism may be related to the regulation of neurotransmitters in brain.
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