文献类型：期刊文献

中文题名：复方地黄颗粒对帕金森病阴虚动风证大鼠多巴胺能神经元生物学功能的影响

英文题名：Effects of Compound Dihuang Granules on biological function of dopaminergic neurons in rats with Parkinson’s disease of Pattern of Yin-Deficiency with Stirring Wind

作者：王行玲[1];梁建庆[1];孙光洁[1];吕子微[1];何建成[2]

第一作者：王行玲

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]上海中医药大学基础医学院,上海201203

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2024

卷号：46

期号：6

起止页码：1828

中文期刊名：中成药

外文期刊名：Chinese Traditional Patent Medicine

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金(82160929);2021年度甘肃省科技厅第十一批省级科技计划自然科学基金(自筹经费)项目(21JR11RA143);敦煌医学与转化教育部重点实验室开放课题(DHYX18-08);2022年度中医学一级学科“岐黄英才”导师专项基金硕导项目(ZYXKSD-202211)。

语种：中文

中文关键词：复方地黄颗粒;帕金森病;阴虚动风证;DJ-1;IP3R;GRP75;VDAC1

外文关键词：Compound Dihuang Granules;Parkinson’s disease;Pattern of Yin-Deficiency with Stirring Wind;DJ-1;IP3R;GRP75;VDAC1

摘要：目的探讨复方地黄颗粒对帕金森病(PD)阴虚动风证大鼠多巴胺(DA)能神经元生物学功能的作用。方法采用6-羟基多巴胺(6-OHDA)脑立体注射法制备PD阴虚动风证动物模型,成模大鼠随机分为模型组、美多芭组(150 mg/kg)和复方地黄颗粒低、中、高剂量组(1.75、3.5、7 g/kg),分别给予相应药物进行干预,正常组、假手术组及模型组给予生理盐水,共灌胃28 d,观察各组大鼠一般情况及神经行为学,HE染色观察黑质组织病理改变,透射电镜技术观察损毁侧黑质内DA能神经元的线粒体结构,免疫组化、Western blot及RT-qPCR法检测DJ-1、IP3R、GRP75、VDAC1表达。结果与正常组、假手术组比较,模型组大鼠旋转圈数增加(P<0.01),游泳评分降低(P<0.01),悬挂时间减少(P<0.01),黑质神经元数量减少,形态受损,黑质内神经元出现线粒体肿胀变性,线粒体嵴消失等损伤,损伤侧黑质DJ-1、IP3R、GRP75、VDAC 1 mRNA和蛋白表达降低(P<0.01);与模型组比较,美多芭组及复方地黄颗粒各剂量组大鼠旋转圈数减少(P<0.01),游泳评分升高(P<0.01),悬挂时间增加(P<0.01),线粒体形态结构损伤减轻,损伤侧黑质DJ-1、IP3R、GRP75、VDAC 1 mRNA和蛋白表达均升高(P<0.05,P<0.01),复方地黄颗粒高剂量效果与美多芭相当(P>0.05)。结论复方地黄颗粒可能通过调控DJ-1、IP3R、GRP75、VDAC1表达促进内质网-线粒体稳态,减轻线粒体损伤,维持DA能神经元生物学功能。
AIM To investigate the effects of Compound Dihuang Granules on biological function of dopaminergic neurons in rats with Parkinson’s disease(PD)of Pattern of Yin-Deficiency with Stirring Wind.METHODS The PD animal model of Pattern of Yin-Deficiency with Stirring Wind established by intracerebral injection of 6-hydroxydopamine(6-OHDA)were randomly divided into the model group,the Midoba group(150 mg/kg)and the low,medium and high dose Compound Dihuang Granules groups(1.75,3.5 and 7 g/kg)for corresponding drug intervention,in contrast to the normal group,the sham operation group and the model group underwent 28-day normal saline administration.The rats had their general condition and neuroethology observed;their pathological changes of substantia nigra observed by HE staining;their mitochondrial structure of dopaminergic neurons in the damaged substantia nigra observed by transmission electron microscopy;and their expressions of DJ-1,IP3R,GRP75 and VDAC1 detected by immunohistochemistry,Western blot and RT-qPCR.RESULTS Compared with the normal group and sham operation group,the model group displayed increased rotational behavirors(P<0.01),decreased swimming time score(P<0.01),decreased hanging time(P<0.01),decreased number of neurons in substantia nigra but more neurons with morphological damage,mitochondrial swelling and degeneration,mitochondrial crista disappearance,and decreased expressions of DJ-1,IP3R,GRP75 and VDAC 1 mRNA and protein in the injured side(P<0.01).Compared with the model group,the Midoba group and the Compound Dihuang Granules groups demonstrated less rotational behavirors(P<0.01),higher swimming time score(P<0.01),longer hanging time(P<0.01),less damage to mitochondrial morphology and structure,and higher expressions of DJ-1,IP3R,GRP 75 and VDAC 1 mRNA and protein in the injured substantia nigra(P<0.05,P<0.01).The high-dose Compound Dihuang Granules presented equivalent efficacy to that of Midoba.CONCLUSION Compound Dihuang Granules may promote endoplasmic reticulum-mitochondria homeostasis,reduce mitochondrial damage and maintain the biological function of dopaminergic neurons by regulating the expressions of DJ-1,IP3R,GRP75 and VDAC1.