文献类型：期刊文献

中文题名：菖蒲郁金汤对多发性抽动症模型大鼠内质网应激PERK/eIF2α/ATF4通路的影响

英文题名：Effects of Changpu Yujin Decoction on PERK/eIF2α/ATF4 endoplasmic reticulum stress pathway in tourette syndrome model rats

作者：黄立威[1];黄爽[1];李梦雪[1];孙铭阳[1];孙可馨[1];魏星[1];史正刚[1];尚菁[1];呼荟茹[1];王倩[1]

第一作者：黄立威

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2025

卷号：50

期号：24

起止页码：6957

中文期刊名：中国中药杂志

外文期刊名：China Journal of Chinese Materia Medica

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金地区科学基金项目(82460951);甘肃中医药大学科研发展基金项目(20YF3FA041);甘肃省高校教师创新基金项目(2024B-098)。

语种：中文

中文关键词：多发性抽动症;菖蒲郁金汤;内质网应激;神经炎症;凋亡

外文关键词：tourette syndrome;Changpu Yujin Decoction;endoplasmic reticulum stress;neuroinflammation;apoptosis

摘要：从内质网应激蛋白激酶R样内质网激酶(PERK)/真核细胞起始因子2α(eIF2α)/激活转录因子4(ATF4)通路探讨菖蒲郁金汤治疗多发性抽动症(tourette syndrome,TS)的可能机制。通过SD大鼠为期7 d腹腔注射3,3′-亚氨基二丙腈(IDPN,300 mg·kg^(-1))建立TS模型,造模成功后,将造模组大鼠随机分为模型组、泰必利组、菖蒲郁金汤组,每组10只。泰必利组予以泰必利(47.91 mg·kg^(-1))灌胃;菖蒲郁金汤组予以菖蒲郁金汤(77.28 g·kg^(-1))灌胃;空白组、模型组给予等体积生理盐水灌胃,每日1次,持续28 d。采用行为学观察对大鼠刻板行为及运动行为进行评分,HE染色法观察大鼠纹状体组织病理形态变化;透射电镜法观察大鼠纹状体组织神经元内质网超微结构;ELISA法检测大鼠纹状体组织白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平;免疫组化法检测大鼠纹状体PERK、eIF2α蛋白表达;免疫荧光法检测大鼠纹状体p-eIF2α、ATF4蛋白共表达;RT-PCR法及Western blot法检测大鼠纹状体PERK/eIF2α/ATF4通路关键因子mRNA及蛋白表达。结果显示,与空白组相比,模型组刻板行为及运动行为评分均升高(P<0.05,P<0.01),纹状体神经元及神经元内质网、线粒体结构病理样改变增加,IL-1β、TNF-α含量升高,PERK、eIF2α、ATF4、C/EBP同源蛋白(CHOP)、Bcl-2相关X蛋白(Bax)mRNA及蛋白表达升高(P<0.05,P<0.01),B细胞淋巴瘤因子2(Bcl-2)mRNA及蛋白表达降低(P<0.05,P<0.01);与模型组相比,泰必利组及菖蒲郁金汤组刻板行为及运动行为评分均降低(P<0.05,P<0.01),纹状体神经元及神经元内质网、线粒体结构病理样改变减轻,IL-1β、TNF-α含量降低,PERK、eIF2α、ATF4、CHOP、Bax mRNA及蛋白表达降低(P<0.05,P<0.01),Bcl-2 mRNA及蛋白表达升高(P<0.05,P<0.01)。综上,菖蒲郁金汤可能通过抑制内质网应激PERK/eIF2α/ATF4通路,改善TS模型大鼠纹状体神经炎症,减少神经元凋亡发挥抗抽动作用。
This study investigated the potential mechanism of Changpu Yujin Decoction in the treatment of tourette syndrome(TS)based on the endoplasmic reticulum stress(ERS)protein kinase R-like ER kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/activating transcription factor 4(ATF4)pathway.A TS model was established by intraperitoneal injection of 3,3'-iminodipropionitrile(IDPN,300 mg·kg^(-1))for 7 days.After successful modeling,the rats were randomly divided into a model group,a Tiapridal group,and a Changpu Yujin Decoction group,with 10 rats in each group.The Tiapridal group received Tiapridal(47.91 mg·kg^(-1))by gavage.The Changpu Yujin Decoction group received Changpu Yujin Decoction(77.28 g·kg^(-1))by gavage.The control and model groups received an equal volume of physiological saline by gavage once daily for 28 days.Stereotyped and locomotor behaviors were scored by behavioral observation.HE staining was used to observe histopathological changes in striatal tissue.Transmission electron microscopy was used to examine endoplasmic reticulum ultrastructure in striatal neurons.ELISA was used to detect the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in striatal tissue.Immunohistochemistry was used to detect PERK and eIF2αprotein expression,and immunofluorescence was used to detect the co-expression of p-eIF2αand ATF4 proteins.RT-PCR and Western blot were employed to detect mRNA and protein expression of key factors in the PERK/eIF2α/ATF4 pathway in the striatum.The results showed that compared with the control group,the model group exhibited significantly increased stereotyped and locomotor behavior scores(P<0.05,P<0.01),aggravated pathological changes in striatal neurons and their endoplasmic reticulum and mitochondrial structures,elevated IL-1βand TNF-αlevels,increased expression of PERK,eIF2α,ATF4,C/EBP-homologous protein(CHOP),and Bcl-2-associated X protein(Bax)mRNA and proteins(P<0.05,P<0.01),and decreased expression of B-cell lymphoma-2(Bcl-2)mRNA and protein(P<0.05,P<0.01).Compared with the model group,both the Tiapridal group and the Changpu Yujin Decoction group showed significantly reduced stereotyped and locomotor behavior scores(P<0.05,P<0.01),alleviated pathological changes in striatal neurons and their endoplasmic reticulum and mitochondrial structures,decreased IL-1βand TNF-αlevels,reduced expression of PERK,eIF2α,ATF4,CHOP,and Bax mRNA and proteins(P<0.05,P<0.01),and increased expression of Bcl-2 mRNA and protein(P<0.05,P<0.01).In conclusion,Changpu Yujin Decoction may exert anti-tic effects by inhibiting the ERS PERK/eIF2α/ATF4 pathway,thereby improving striatal neuroinflammation and reducing neuronal apoptosis in TS model rats.