文献类型：期刊文献

中文题名：菖蒲郁金汤对多发性抽动症大鼠线粒体自噬及PINK1/Parkin信号通路的影响

英文题名：Effects of Changpu Yujin Decoction on mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome

作者：黄爽[1];闫亚丽[1];梅镐[1];姚景曦[1];薛付春[1];尚菁[1];唐彦[2];史正刚[1]

第一作者：黄爽

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]云南中医药大学第一临床医学院,云南昆明650500

第一机构：甘肃中医药大学中医临床学院

年份：2025

卷号：47

期号：10

起止页码：3225

中文期刊名：中成药

外文期刊名：Chinese Traditional Patent Medicine

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(81960886,82460951);甘肃中医药大学科研发展基金项目(20YF3FA041)。

语种：中文

中文关键词：菖蒲郁金汤;多发性抽动症;PINK1/Parkin信号通路;神经元凋亡;纹状体;线粒体自噬

外文关键词：Changpu Yujin Decoction;Tourette syndrome;PINK1/Parkin signaling pathway;neuron apoptosis;striatum;mitophagy

摘要：目的探讨菖蒲郁金汤对多发性抽动症(TS)大鼠纹状体线粒体自噬和PINK1/Parkin信号通路的影响。方法36只SPF级雄性SD大鼠随机分为空白组(9只)和TS组(27只),TS组大鼠每天腹腔注射亚氨基二丙腈(300 mg/kg),连续7 d以建立TS模型。造模成功后,将TS大鼠随机分为模型组、泰必利组(47.91 mg/kg)和菖蒲郁金汤组(77.28 g/kg),并分别予以相应药物干预28 d。给药结束后,各组大鼠进行行为学评分,HE染色观察纹状体病理改变,透射电子显微镜(TEM)观察纹状体超微结构变化,TUNEL染色评价神经元凋亡水平,ELISA法检测纹状体ROS水平,免疫荧光染色(IF)检测纹状体PINK1与LC3B共表达,RT-qPCR和Western blot法检测纹状体PINK1、Parkin、Beclin-1、P62、LC3B(LC3B-Ⅱ/Ⅰ)mRNA、蛋白表达。结果与空白组比较,模型组大鼠行为学评分、神经元凋亡率及纹状体ROS水平均升高(P<0.01),纹状体神经元和线粒体发生损伤,纹状体PINK1、Parkin、Beclin-1、LC3B(LC3B-Ⅱ/Ⅰ)mRNA、蛋白表达均降低(P<0.01),P62 mRNA、蛋白表达升高(P<0.01);与模型组比较,泰必利组和菖蒲郁金汤组大鼠行为学评分、神经元凋亡率及纹状体ROS水平均降低(P<0.01),纹状体线粒体和神经元病理损伤改善,纹状体PINK1、Parkin、Beclin-1 mRNA、蛋白表达均升高(P<0.05,P<0.01),P62 mRNA、蛋白表达降低(P<0.01);菖蒲郁金汤组大鼠纹状体LC3B mRNA、LC3B-Ⅱ/Ⅰ蛋白表达升高(P<0.05,P<0.01)。结论菖蒲郁金汤对TS大鼠的改善作用可能与调节PINK1/Parkin信号通路激活线粒体自噬、改善线粒体功能、降低ROS水平,进而保护神经元相关。
AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3’-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P<0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P<0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰratio)in the striatum(P<0.01);markedly upregulated P62 mRNA and protein expressions(P<0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P<0.01);decreased neuronal apoptosis rate and lower ROS levels(P<0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P<0.05,P<0.01);and decreased P62 mRNA and protein expressions(P<0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰprotein ratio in striatum(P<0.05,P<0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.