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,r
作者
王行玲
梁建庆
孙光洁
吕子微
何建成
WANG Xing-ling;LIANG Jian-qing;SUN Guang-jie;L Zi-wei;HE Jian-cheng(College of Basic Medical Sciences,Gansu University of Chinese Medicine,Lanzhou 730000,China;School of Basic Medical Sciences,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中成药》
CAS
CSCD
北大核心
2024年第6期1828-1835,共8页
Chinese Traditional Patent Medicine
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)。
