香青兰总黄酮通过介导自噬改善帕金森病模型小鼠的神经损伤的作用  

The effect of total flavonoids of Dracocephalummoldavica L.on improving nerve injury in Parkinson's disease model mice by mediating autophagy

作　　者：索耀文 莫超然 杨占君[3] SUO Yaowen;MO Chaoran;YANG Zhanjun(2020 Graduate Student of School of Preclinical and Forensic Medicine,Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014040,China;Deyang Hospital of Integrated Traditional Chinese and Western Medicine;Department of Human Anatomy,Baotou Medical College,Inner Mongolia University of Science and Technology)

机构地区：[1]内蒙古科技大学包头医学院基础医学与法医学院,内蒙古包头014040 [2]德阳市中西医结合医院 [3]内蒙古科技大学包头医学院人体解剖学教研室

出　　处：《包头医学院学报》2023年第12期1-7,共7页Journal of Baotou Medical College

基　　金：内蒙古自治区自然科学基金面上项目(2020MS08011)。

摘　　要：目的:研究中药香青兰总黄酮(TFD)改善帕金森病模型小鼠神经损伤的作用机制。方法:120只小鼠被随机分为正常对照组20只和观察组100只,观察组小鼠腹腔注射30 mg/(kg·d)MPTP以制备PD小鼠模型,对照组小鼠腹腔注射等体积生理盐水,连续7 d后再将观察组小鼠随机分为5组,分别为模型组和TFD治疗组25、50、75、100 mg/(kg·d):。治疗组按照小鼠的体重灌胃给药,正常对照组和模型组小鼠给予等容量的生理盐水,连续1个月。通过行为学实验评价小鼠运动功能,通过免疫荧光组织化学技术检测小鼠中脑黑质区组织细胞酪氨酸羟化酶(TH)和选择性自噬接头蛋白(P62)阳性染色的细胞数,采用荧光定量PCR和Western-blot技术检测小鼠黑质区组织的微管相关蛋白1轻链3β(LC3B)、P62、自噬效应蛋白(Beclin1)和TH mRNA和蛋白表达水平。结果:TFD治疗显著增加PD模型小鼠的悬挂运动评分、运动距离和下落潜伏期(P<0.05);TFD治疗增加PD模型小鼠黑质区组织表达P62和TH的阳性染色细胞数,TFD治疗增加PD模型小鼠黑质区组织表达PINK1、Parkin、P62、和TH蛋白的阳性染色细胞数(P<0.05)。结论:TFD可能通过上调LC3B、P62、Beclin1改善自噬,促进多巴胺能神经元受损线粒体及其他细胞器的清除,从而对MPTP诱导的PD模型小鼠产生神经保护作用。Objective:To study the mechanism of total flavonoids of Dracocephalummoldavica L.(TFD)on improving nerve injury in Parkinson's disease model mice.Methods:A total of 120 mice were randomly divided into normal control group(n=20)and observation group(n=100).The mice in the observation group were intraperitoneally injected with 30 mg/(kg·d)PTP to prepare PD mouse model,and the mice in the control group were intraperitoneally injected with the same volume of normal saline.After 7 days,the mice in the observation group were randomly divided into 5 groups:model group and TFD treatment group 25,50,75,100 mg/(kg·d):.The mice in the treatment group were given intragastric administration according to the body weight of the mice,and the mice in the normal control group and the model group were given an equal volume of normal saline for 1 month.The motor function of mice was evaluated by behavioral experiments.The number of positive staining cells of tyrosine hydroxylase(TH)and selective autophagy adaptor protein(P62)in the substantia nigra of mice was detected by immunofluorescence histochemistry.The expression levels of microtubule-associated protein 1 light chain 3β(LC3B),P62,autophagy effector protein(Beclin1)and TH mRNA and protein in the substantia nigra of mice were detected by fluorescence quantitative PCR and Western-blot.Results:TFD treatment significantly increased the suspension motion score,movement distance and fall latency of PD model mice(P<0.05).TFD treatment increased the number of positive staining cells expressing P62 and TH in the substantia nigra of PD model mice,and TFD treatment increased the number of positive staining cells expressing PINK1,Parkin,P62 and TH proteins in the substantia nigra of PD model mice(P<0.05).Conclusion:TFD may improve autophagy by up-regulating LC3B,P62 and Beclin1,and promote the clearance of damaged mitochondria and other organelle of dopaminergic neurons,thus producing neuroprotective effects on MPTP-induced PD model mice.

关 键 词：香青兰总黄酮 帕金森病 自噬 小鼠 

分 类 号：R285.5[医药卫生—中药学]