艾司西酞普兰对帕金森病大鼠运动行为学及黑质多巴胺神经元的影响  

Effect of escitalopram on the motor behavior and dopamine neurons in the substantia nigra of Parkinson’s disease rats

作　　者：赵文梅 杨朝霞 黄效模[2] 邱男[2] 张颖粤 陈中玮 吴光洁 刘承铭 李珏 田锦勇[2] ZHAO Wen-mei;YANG Chao-xia;HUANG Xiao-mo;QIU Nan;ZHANG Ying-yue;CHEN Zhong-wei;WU Guang-jie;LIU Cheng-ming;LI Jue;TIAN Jin-yong(School of Clinical Medicine,Zunyi Medical University,Zunyi 563003,Guizhou Province,China;Department of Emergency Medicine,Guizhou Provincial People’s Hospital,Guiyang 550004,Guizhou Province,China)

机构地区：[1]遵义医科大学临床学院,贵州遵义563003 [2]贵州省人民医院急诊内科,贵州贵阳550004

出　　处：《中国临床药理学杂志》2022年第3期233-237,共5页The Chinese Journal of Clinical Pharmacology

基　　金：贵州省科计划基金资助项目([2020]1Z059)。

摘　　要：目的观察艾司西酞普兰(ESC)对帕金森病(PD)大鼠运动行为学及黑质多巴胺神经元的影响,并探讨可能机制。方法将30只PD大鼠随机分为PD组、ESC组、ESC+LY294002组,各10只。另10只仅做假手术,设为Sham组。造模成功后,ESC组给予ESC 10 mg·kg^(-1)(溶于生理盐水),灌胃;ESC+LY294002组给予ESC 10 mg·kg^(-1),灌胃,同时给予0.5 mg·kg^(-1) LY294002,静脉注射;Sham组、PD组给予等体积生理盐水灌胃及静脉注射。4组大鼠每天给药1次,连续干预4周。观察大鼠运动行为学;检测黑质丙二醛(MDA)、超氧化物歧化酶(SOD)含量;以免疫组化法检测黑质酪氨酸羟化酶(TH)表达;以蛋白质印迹法检测黑质磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、p-Akt、哺乳动物西罗莫司靶蛋白(mTOR)、p-mTOR蛋白表达。结果Sham组、PD组、ESC组、ESC+LY294002组的旷场实验跨格次数分别为(31.92±4.10),(4.44±0.62),(23.21±3.12),(15.73±7.33)次,旋转圈数分别为(1.53±0.16),(9.12±1.23),(4.27±0.57),(6.65±0.75)r·min^(-1),黑质MDA含量为(1.31±0.28),(5.02±0.69),(2.50±0.45),(3.42±0.51)nmol·mg^(-1) prot;黑质TH平均光密度值分别为2.01±0.39,0.19±0.02,1.03±0.25,0.58±0.09。上述指标及各蛋白表达量,PD组与Sham组比较,ESC组与PD组比较,ESC+LY294002组与ESC组比较,差异均有统计学意义(均P<0.05)。结论ESC可改善PD大鼠运动行为学、黑质氧化应激及病理学变化,保护黑质多巴胺神经元,可能通过激活PI3K/Akt信号通路来实现。Objective To observe the effect of escitalopram(ESC)on the motor behavior and substantia nigra dopamine neurons in Parkinson’s disease(PD)rats,and to explore the possible mechanism.Methods Thirty PD rats were randomly divided into PD group,ESC group,ESC+LY294002 group,10 rats in each group.Ten only underwent sham operation and were set as sham group.After successful modeling,ESC group was given ESC 10 mg·kg^(-1) dissolved in saline by gavage,ESC+LY294002 group was given ESC 10 mg·kg^(-1)(dissolved in saline)by gavage,and LY2940020.5 mg·kg^(-1) was injected intravenously.Sham group and PD group was given the same volume of normal saline,intragastrically and intravenously.Once a day,continuous intervention for 4 weeks.The behavior of rats were observed.The content of malondialdehyde(MDA)and superoxide dismutase(SOD)in the substantia nigra of the brain were detected.The expression of substantia nigra tyrosine hydroxylase(TH)were detected by immunohistochemical.The expression of substantia nigra phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),p-Akt,mammalian target of rapamycin(mTOR),and p-mTOR protein were detected by Western blotting.Results The straddle times of the open field experiment in sham group,PD group,ESC group,and ESC+LY294002 group were(31.92±4.10),(4.44±0.62),(23.21±3.12),(15.73±7.33),the number of rotations were(1.53±0.16),(9.12±1.23),(4.27±0.57),(6.65±0.75)r·min^(-1),the substantia nigra MDA content were(1.31±0.28),(5.02±0.69),(2.50±0.45),(3.42±0.51)nmol·mg^(-1) prot,the average optical density values of the substantia nigra TH were 2.01±0.39,0.19±0.02,1.03±0.25,0.58±0.09.The above indicators and the expression levels of each protein,the differences between PD group and sham group,ESC group and PD group,ESC+LY294002 group and ESC group were statistically significant(all P<0.05).Conclusion ESC can improve the motor behavior,substantia nigra oxidative stress and pathological changes in PD rats,and protect substantia nigra dopamine neurons,which may be achieved by activa

关 键 词：帕金森病 艾司西酞普兰 运动行为学 黑质多巴胺神经元 

分 类 号：R97[医药卫生—药品]