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肠-肝-脑轴DJ-1、IP3R、GRP75、VDAC1表达的影响

英文题名：Effects of Compound Dihuang Granules on the Expressions of DJ-1,IP3R,GRP75 and VDAC1 in Gut-Liver-Brain Axis in Rats with Parkinson Disease with Yin Deficiency and Wind Movement Syndrome

作者：王行玲[1];孙光洁[1];吕子微[1];何建成[2];梁建庆[1]

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：31

期号：10

起止页码：121

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(82160929);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);甘肃中医药大学中医学一级学科“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：帕金森病;阴虚动风证;复方地黄颗粒;肠-肝-脑轴;大鼠

外文关键词：Parkinson disease;yin deficiency and wind movement syndrome;compound Dihuang Granules;gut-liver-brain axis;rats

摘要：目的观察复方地黄颗粒对帕金森病(PD)阴虚动风证大鼠肝脏和结肠组织DJ-1、肌醇1,4,5-三磷酸受体(IP3R)、葡萄糖调节蛋白75(GRP75)、电压依赖性阴离子通道1(VDAC1)表达的影响。方法采用右侧黑质注射6-羟基多巴胺法制备PD阴虚动风证大鼠模型,将造模成功的65只大鼠随机分为模型组、美多芭组(美多芭150 mg/kg)和中药低、中、高剂量组(复方地黄颗粒1.75、3.5、7 g/kg),每组13只。另取13只未造模大鼠为正常对照组、13只仅注射抗坏血酸溶液大鼠为假手术组。各药物组予相应药物灌胃,正常对照组、假手术组和模型组予生理盐水灌胃,每日1次,连续28 d。观察大鼠神经行为学变化,HE染色观察肝组织、结肠组织形态,免疫组化染色、RT-PCR、Western blot分别检测肝组织和结肠组织DJ-1、IP3R、GRP75、VDAC1蛋白及mRNA表达。结果与正常对照组和假手术组比较,模型组大鼠旋转圈数增加,肝组织颗粒样变性,细胞胞质疏松,少量肝细胞脂肪变性,结肠黏膜层及黏膜下层水肿,结缔组织疏松,有少量淋巴细胞浸润,较多血管扩张,肝组织和结肠组织DJ-1、IP3R、GRP75、VDAC1蛋白及m RNA表达均明显降低(P<0.01);与模型组比较,美多芭组及中药各剂量组大鼠旋转圈数减少,肝细胞轻度颗粒样变性,胞质疏松,肝索排列较整齐,结肠轻度水肿,有少量淋巴细胞、粒细胞浸润,少量血管扩张,肝组织和结肠组织DJ-1、IP3R、GRP75、VDAC1蛋白及mRNA表达均明显升高(P<0.05),中药高剂量组变化最明显,与美多芭组比较差异无统计学意义(P>0.05)。结论复方地黄颗粒可能通过调节肝组织和结肠组织DJ-1、IP3R、GRP75、VDAC1表达恢复内质网-线粒体稳态,改善肠-肝-脑轴线粒体功能,保护多巴胺能神经元,延缓PD进程。
Objective To observe the effect of compound Dihuang Granules on the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue of Parkinson disease(PD)rats with yin deficiency and wind movement syndrome.Methods 6-Hydroxydopamine was used to inject into the right substantia nigra to prepare PD with yin deficiency and wind movement syndrome rats model.65 rats that successfully modeled were randomly divided into model group,madopar group(madopar 150 mg/kg)and TCM low-,medium-and high-dosage groups(compound Dihuang Granules 1.75,3.5,7 g/kg),with 13 rats in each group;another 13 rats without intervention were selected as the normal control group,and 13 rats were only injected with ascorbic acid solution as sham-operation group.The administration groups were given corresponding drugs by gavage,and the normal control group,sham-operation group and model group were given normal saline by gavage,once a day for 28 consecutive days.The neurobehavioral changes of rats were observed,and the morphology of liver tissue and colonic tissue were observed by HE staining,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue were detected by immunohistochemical staining,Western blot and RT-PCR,respectively.Results Compared with the normal control group and the sham-operation group,the number of rotation circles of rats in the model group increased,with granular degeneration of liver tissue,loose cytoplasm of cells,slight hepatic steatosis,edema of colonic mucosal and submucosal layers,loose connective tissue,infiltration of a small number of lymphocytes,and significant vascular dilation,the expressions of DJ-1,IP3R,GRP75 and VDAC1 protein and mRNA in liver and colonic tissue were significantly decreased(P<0.01).Compared with the model group,the number of rotation circles of rats in madopar group and TCM groups were significantly decreased,with mild granular degeneration of liver cells,loose cytoplasm,orderly arrangement of hepatic cords,mild edema of the colon,a small amount of lymphocyte and granulocyte infiltration,and a small amount of vascular dilation,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue significantly increased(P<0.05).The TCM high-dosage group showing the most obvious changes,there was no statistical significance with the madopar group(P>0.05).Conclusion Compound Dihuang Granules may restore endoplasmic reticulum-mitochondria homeostasis,improve gut-liver-brain axis mitochondrial function,protect dopamine neurons,and delay PD by regulating the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver tissue and colonic tissue.