肉桂醛对MPTP诱导的亚急性帕金森模型小鼠的神经保护机制研究  

Neuroprotective effect of cinnamaldehyde in MPTP-induced mouse model of subacute Parkinson′s disease

作　　者：吴宿慧[1] 史亚瑾 安迎凤 赵丹丹[1] 李寒冰[1] 李根林[1] WU Su-hui;SHI Ya-jin;AN Ying-feng;ZHAO Dan-dan;LI Han-bing;LI Gen-lin(Henan University of Chinese Medicine,Henan Zhong-jing Recipe Health and Aging Industry Engineering Research Center,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,河南省仲景方药健康衰老产业工程研究中心,郑州450046

出　　处：《中国中药杂志》2022年第23期6485-6493,共9页China Journal of Chinese Materia Medica

基　　金：河南省科技协同创新专项(XTCX2021-15);河南省中医药科学研究专项(20-21ZY1041)。

摘　　要：为了研究肉桂醛(cinnamaldehyde,CA)对1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的亚急性帕金森病(Parkinson′s disease,PD)模型小鼠的神经保护作用机制,72只雄性C57BL/6小鼠随机分为空白组,模型组,美多芭组(0.1 mg·g^(-1)),肉桂醛低、中、高剂量组(0.15、0.3、0.6 mg·g^(-1)),除空白组外,其余各组腹腔注射MPTP(0.03 mg·g^(-1)),连续5 d,复制亚急性PD小鼠模型,造模同时治疗组灌胃给予药物共19 d。第0、12、19天进行旷场、爬杆及转棒实验,实验结束后,处死小鼠并取脑,测定小鼠脏器指数,HE染色测CA对黑质(substantia nigra,SN)细胞数目的影响,免疫组化法测SN内酪氨酸羟化酶(tyrosine hydroxylase,TH)、α-突触核蛋白(synuclein,α-Syn)表达水平,蛋白印迹(Western blot,WB)法测SN内TH、α-Syn蛋白表达水平。结果表明注射MPTP后,小鼠出现弓背竖毛、尾僵直、行动迟缓、震颤等异常行为表现,跨格次数、站立次数减少,尿便次数增多,爬杆时间延长,停留转棒时间缩短,SN区出现明显的神经元受损,可见细胞数量显著减少,结构排列紊乱,部分胞体皱缩,体积变小,TH平均灰度降低,α-Syn平均灰度增加,表明PD模型复制成功。CA干预治疗后,对PD模型动物有明显疗效,跨格次数、站立次数增加,尿便次数减少,爬杆时间缩短,停留转棒时间延长,SN区神经细胞数量明显增多,可见较少数量的固缩细胞,明显减轻SN内TH的减少和α-Syn的过表达,从而减轻MPTP所致的多巴胺能神经元损伤,以0.3 mg·g^(-1)剂量为最佳,可为CA新产品的开发提供科学依据。This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA)in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson′s disease(PD)and the mechanism.To be specific,male C57BL/6 mice(n=72,SPF)were randomized into control group,model group,positive control(madopar 0.1 mg·g^(-1))group,and low-dose,me-dium-dose,and high-dose CA groups(0.15,0.30,0.60 mg·g^(-1)).MPTP(intraperitoneal injection,0.03 mg·g^(-1),once a day for 5 days)was used to induce subacute PD in mice except for the control group.The administration began from the day of modeling and lasted 19 days.On the 0 th,12 th,and 19 th day,the open field test,pole test,and rotarod test were carried out.After the tests,the mice were killed and brains were separated.In addition,the organ index was measured.The number of cells in substantia nigra(SN)in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE)staining.The levels of tyrosine hydroxylase(TH)-andα-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining,and the protein levels of TH andα-Syn in SN by Western blot.The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair,arched back,rigidity of the tail,slow movement,and tremor,decreased number of crossings and rearing,increased frequency of urination and defecation,longer time of pole climbing,and shorter time of staying on the rotating rod.In addition,the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking.In addition,the average optical density of TH in SN decreased and that ofα-Syn increased.All these suggested the successful modeling.CA displayed obvious therapeutic effect on the PD mice,as manifested by the increased number of crossings and rearing,decreased frequency of urination and defecation,shorter time of climbing pole,longer time of staying on the rotating rod,and more neuron cells in the SN with a few pykno-tic cells.Moreover,CA

关 键 词：帕金森病 肉桂醛 黑质 Α-突触核蛋白 运动障碍 

分 类 号：R285.5[医药卫生—中药学]