许苗菁 钟花 赵振强 陈薪旭 冯晓丽 张海英 王埮

(海南医学院 1第一附属医院神经内科，海南 海口 570102;2海南热带脑科学研究与转化重点实验)

Sodium butyrate improving the motor function and decreasing the anxiety-like behavior in mice damaged by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)

XU Miao-Jing, ZHONG Hua, ZHAO Zhen-Qiang,etal.

Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan,China

【Abstract】ObjectiveTo explore the influences of sodium butyrate (NaB) on motor function and anxious behavior of PD model.MethodsMice were divided into control, model, NaB groups. Control group of mice were intrapertioneally injected with saline for 28 days, model group of mice were injected with MPTP intrapertioneally for 14 days and continued to inject with saline for 14 days, NaB group of mice were injected with MPTP intrapertioneally for 14 days and continued to inject with NaB for 14 days. The behaviour experiment of mice were measured by rotarod test, pole test and open field. Western blot and immunochemistry were used to detect expression of TH protein in brains of mice.ResultsIn the rotarod test, the time on the rotarod of model mice were shorter than that of normal group, however the time of NaB group were increased significantly than that of model group. In pole test, compared with normal mice, the time to climb pole of model mice were significantly prolonged. In contrast, the time of NaB group of mice were shorter than that of model group. In open field, the numbers of crossing the middle region of model mice were less than that of control group, but were increased in NaB group. In addition, the total distance of model group was reduced compared with control group, while NaB group of mice were increased. In Western blot and immunochemistry test, compared with control group, TH expression of model mice was decreased, while it was increased in NaB group.ConclusionsNaB could increase the expression of TH in brain of MPTP model mice, reduce the loss of dopamine neurons, and improve the motor function and decrease the anxiety-like behavior in mice.

【Keywords】 Parkinson disease; Sodium butyrate;1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Motor function; Anxiety-like behavior

中脑黑质多巴胺神经元缺失是帕金森病(PD)病理特点〔1〕。PD症状分运动症状和非运动症状，非运动症状包括焦虑，抑郁、睡眠障碍等〔2〕。目前PD因机制未能完全明确，针对性的治疗一直是研究热点。丁酸钠(NaB)是一种去乙酰化酶抑制剂，也是一种重要神经保护剂，其对多种神经系统疾病包括PD具有一定的保护作用〔3～7〕。目前对丁酸钠改善PD小鼠模型非运动症状，尤其是焦虑行为的改善作用未能完全明确，本文通过5，1-甲基-4苯基-1，2，3，6-四氢吡啶(MPTP )构建 PD 小鼠模型，探究 NaB 通过减少多巴胺神经元丢失，进一步对PD小鼠运动及部分非运动症状的影响及作用。

1 材料与方法

1.1动物与材料 动物：150只SPF级C57小鼠，体重(20.09±0.39)g，8～10周龄，由华中农业大学提供，室温21～23℃、湿度55%～60%SPF级动物房养殖，12 h昼夜节律，自然光照，自由饮水进食。小鼠随机分为正常组、模型组和给药组各50只。主要材料：MPTP及NaB粉末购自美国Sigma；酪氨酸羟化酶(TH)抗体及β肌动蛋白(β-actin)抗体购自美国CST；苯甲基磺酰氟(PMSF)、蛋白裂解液、二喹啉甲酸(BCA)蛋白测量试剂盒、电化学发光液(ECL)购自碧云天；二氨基联苯胺(DAB)显色试剂盒购自北京中杉生物有限公司；辣根过氧化物酶(HRP)标记山羊抗兔IgG；聚偏二氟乙烯(PVDF)膜购自美国Millipore；全自动数码凝胶图像分析系统购自天能科技有限公司；病理切片机购自莱卡；正置光学显微镜购自日本奥林巴斯；小鼠旷场实验轨迹分析仪器购自上海欣软信息科技有限公司；……