藏药七十味珍珠丸对6-OHDA帕金森模型大鼠的神经保护作用  

Neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill on6-OHDA Parkinson’s disease model rats

作　　者：崔海燕 宋丹[1] 李红艳 李捷 赵鑫杰[1] 赵健黎[1] 张梦如[1] 程勇 CUI Haiyan;SONG Dan;LI Hongyan;LI Jie;ZHAO Xinjie;ZHAO Jianli;ZHANG Mengru;CHENG Yong(School of Medicine,Xizang Minzu University,Xianyang 712082;Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region,Xizang Minzu University,Xianyang 712082;Key Laboratory of High Altitude Environment and Genes Related to Disease of Tibet Autonomous Region,Xizang Minzu University,Xianyang 712082;Engineering Center for Tibetan Medicine Testing Technology,Ministry of Education,Xizang Minzu University,Xianyang 712082;College of Life and Environmental Sciences,Minzu University of China,Beijing 100081,China)

机构地区：[1]西藏民族大学医学院,陕西咸阳712082 [2]西藏民族大学高原相关疾病分子机制与干预研究重点实验室,陕西咸阳712082 [3]西藏民族大学高原环境与疾病相关基因研究重点实验室,陕西咸阳712082 [4]西藏民族大学藏药检测技术教育部工程研究中心,陕西咸阳712082 [5]中央民族大学生命与环境科学学院,北京100081

出　　处：《西安交通大学学报(医学版)》2025年第1期190-196,共7页Journal of Xi’an Jiaotong University(Medical Sciences)

基　　金：西藏自治区自然科学基金资助项目(No.ZRKX2020000075);西藏自治区教育厅藏医药区域协同创新中心项目(No.2018XTCXOO3);西藏民族大学校内科研项目(No.22MDY08)。

摘　　要：目的 探讨藏药七十味珍珠丸(RNSP)对6-羟基多巴胺(6-OHDA)诱导的帕金森模型(PD)大鼠神经保护作用及其相关机制。方法 48只雄性SD大鼠随机分为对照组、模型组、模型+RNSP低剂量组(90 mg/kg)、模型+RNSP中剂量组(180 mg/kg)、模型+RNSP高剂量组(360 mg/kg)及模型+美多芭组(50 mg/kg),每组8只。除对照组外,其余大鼠采用6-OHDA纹状体单点注射法制作PD模型,造模完成后各组大鼠灌胃给药,对照组及模型组大鼠给予等体积生理盐水,每日1次,共4周。造模完成后第2、4周进行阿扑吗啡诱导的大鼠旋转实验,末次旋转实验结束后次日进行旷场实验观察动物行为;行为学实验结束后免疫组化法进行大鼠黑质致密部酪氨酸羟化酶(TH)染色并对阳性神经元计数;Western blotting法检测大鼠黑质凋亡相关蛋白Bcl-2、BAX、Caspase-3以及纹状体P38、P-P38、ERK、P-ERK、JNK、P-JNK蛋白表达。结果 与对照组相比,模型组大鼠造模后第2周及第4周旋转频率及旋转大鼠百分比均显著增加,旷场活动距离、平均速度及穿格次数显著减少,静止时间显著增加,黑质TH阳性神经元数目显著减少,BAX、Caspase-3蛋白表达显著升高,Bcl-2蛋白表达显著降低,纹状体P-JNK/JNK、P-P38/P38、P-ERK/ERK比值显著升高;与模型组相比,RNSP给药2周后低、中、高剂量组大鼠旋转频率及旋转大鼠百分比无显著变化,RNSP给药4周后高剂量组大鼠旋转频率及低、中剂量组旋转大鼠百分比显著降低,大鼠旷场活动距离、平均速度及穿格次数显著增加,静止时间显著缩短,黑质TH阳性神经元数目显著增加,Bax、Caspase-3蛋白表达显著降低,Bcl-2蛋白表达显著升高,纹状体P-P38/P38、P-JNK/JNK、P-ERK/ERK比值显著降低。结论 RNSP可改善PD大鼠运动能力,减少DA神经元丢失,其机制可能与抑制P38/JNK/ERK信号通路,减少中脑神经元凋亡有关。Objective To investigate the neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill(RNSP)on 6-hydroxydopamine(6-OHDA)induced Parkinson’s disease model rats and its related mechanism.Methods Totally 48 male SD rats were randomly divided into control group,model group,model plus low-dose RNSP group(90 mg/kg),model plus medium-dose RNSP group(180 mg/kg),model plus high-dose RNSP group(360 mg/kg),and model plus madopar group(50 mg/kg),with 8 rats in per group.Except for the control group,the other rats were treated with 6-OHDA single injection into the striatum to establish the PD model.Each group was given intragastric administration after modeling and the control group and model group were given an equal volume of saline once a day for 4 weeks.The rats were subjected to apomorphine-induced rotation,experiments at the 2nd and 4th week after the completion of modeling,and the open field experiment was conducted the next day after the last rotation experiment to observe the animal behavior.After the behavioral experiment,the rats were stained with tyrosine hydroxylase(TH)in the substantia nigra pars compacta by immunohistochemical method and the positive neurons were counted.The protein levels of Bcl-2,BAX,Caspase-3 in substantia nigra and P38,P-P38,ERK,P-ERK,JNK,P-JNK in the striatum were detected by Western blotting.Results Compared with the control group,the rotation frequency and percentage of rotating rats in the model group increased significantly at the 2nd and 4th weeks after modeling;the open field active distance,average speed and times of crossing the grid were significantly decreased;and the rest time was significantly increased.While the number of TH positive neurons in the substantia nigra was significantly decreased,the BAX and Caspase-3 protein levels were increased significantly,Bcl-2 was decreased significantly,the ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly increased in PD group.Compared with the model group,the rotation frequency and percentage of rotating

关 键 词：藏药 七十味珍珠丸 帕金森症 P38/JNK/ERK信号通路 凋亡 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R29[医药卫生—临床医学] R363.2