文献类型：期刊文献

中文题名：基于PI3K/AKT/mTOR信号通路探讨复方地黄颗粒对帕金森病阴虚动风证大鼠的影响

英文题名：Exploration on the Effects of Compound Dihuang Granules on Parkinson Disease Rats with Yin Deficiency and Wind Movement Syndrome Based on PI3K/AKT/mTOR Signaling Pathway

作者：张之菁[1];梁建庆[1,2]

第一作者：张之菁

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]敦煌医学与转化教育部重点实验室,甘肃兰州730000

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：7

起止页码：83

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(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(ZYXKSD-202211);甘肃中医药大学“中医老年病学”学科建设项目(2022-3)。

语种：中文

中文关键词：复方地黄颗粒;帕金森病;阴虚动风证;自噬;PI3K/AKT/mTOR信号通路

外文关键词：compound Dihuang Granules;Parkinson disease;yin deficiency and wind movement syndrome;autophagy;PI3K/AKT/mTOR signaling pathway

摘要：目的观察复方地黄颗粒对帕金森病(PD)阴虚动风证大鼠黑质PI3K/AKT/mTOR信号通路的影响,探讨其治疗PD的作用机制。方法通过向黑质注射6-羟多巴胺制备PD阴虚动风证大鼠模型。将大鼠随机分为对照组、假手术组、模型组、美多芭组和复方地黄颗粒低、中、高剂量组,每组10只。各组分别予相应溶液灌胃,连续28 d。检测大鼠神经行为学变化,HE染色观察黑质形态变化,RT-qPCR检测受损黑质PI3K、AKT、mTOR、p62、LC3BmRNA表达,免疫组化检测受损黑质p-PI3K、p-AKT、p-mTOR表达,Western blot检测受损黑质p-PI3K、PI3K、p-AKT、AKT、p-mTOR、mTOR、p62、LC3B蛋白表达。结果与对照组和假手术组比较,模型组大鼠旋转圈数增加,爬杆时间延长,悬挂时间及移动格数减少(P<0.01);黑质神经元排列紊乱,胞核固缩、结构模糊;受损黑质PI3K、AKT、mTOR、p62 mRNA表达升高,p-PI3K、p-AKT、p-mTOR、p62蛋白表达升高,LC3B mRNA和LC3BⅡ/Ⅰ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,爬杆时间缩短,悬挂时间及移动格数增加(P<0.01);黑质神经元数目增多,结构形态明显改善;受损黑质PI3K、AKT、mTOR、p62 mRNA表达降低,p-PI3K、p-AKT、p-mTOR、p62蛋白表达降低,LC3B mRNA和LC3BⅡ/Ⅰ蛋白表达升高(P<0.05,P<0.01),以复方地黄颗粒高剂量组作用最明显(P<0.05,P<0.01),与美多芭组差异无统计学意义(P>0.05)。结论复方地黄颗粒可能通过抑制PI3K/AKT/mTOR信号通路增强受损黑质自噬能力,保护多巴胺能神经元,从而治疗PD。
Objective To explore the effects of compound Dihuang Granules on the Parkinson disease(PD)rats with yin deficiency and wind movement syndrome based on PI3K/AKT/mTOR signaling pathway;To explore the mechanism of its mechanism on PD.Methods A rat model of PD with yin deficiency and wind movement syndrome was prepared by injecting 6-OHDA to substantia nigra.The rats were randomly divided into control group,sham-operation group,model group,madopar group,and compound Dihuang Granules low-,medium-,and high-dosage groups,with 10 rats in each group.Each group was treated with corresponding solution by gavage for 28 consecutive days.After treatment,the neurobehavioral changes of rats were detected,HE staining was used to observe the pathological changes in substantia nigra,and RT-qPCR was used to detect the expressions of PI3K,AKT,mTOR,p62 and LC3B mRNA in damaged substantia nigra,immunohistochemistry was used to detect the expressions of p-PI3K,p-AKT and p-mTOR in damaged substantia nigra,Western blot was used to detect the expressions of p-PI3K,PI3K,p-AKT,AKT,p-mTOR,mTOR,p62 and LC3B protein in damaged substantia nigra.Results Compared with the control group and sham-operation group,the model group rats showed an increase in the number of rotations,an extension of pole climbing time,and a decrease in suspension time and number of moving grids(P<0.01),with disordered arrangement of substantia nigra neurons,nuclear pyknosis,and blurred structure,the expressions of PI3K,AKT,mTOR and p62 mRNA in damaged substantia nigra increased,the protein expressions of p-PI3K,p-AKT,p-mTOR and p62 increased,and the expressions of LC3B mRNA and LC3BⅡ/Ⅰprotein decreased(P<0.01).Compared with the model group,the number of rotations and pole climbing time of rats in madopar group and compound Dihuang Granules groups decreased,while the suspension time and number of moving grids increased(P<0.01),with increased number of substantia nigra neurons and improved structural morphology,the expressions of PI3K,AKT,mTOR and p62 mRNA in damaged substantia nigra decreased,the protein expressions of p-PI3K,p-AKT,p-mTOR and p62 decreased,and the expressions of LC3B mRNA and LC3BⅡ/Ⅰprotein increased(P<0.05,P<0.01).The compound Dihuang Granules high-dosage group had the most significant effect(P<0.05,P<0.01),and there was no statistically difference compared with the madopar group(P>0.05).Conclusion Compound Dihuang Granules may enhance damaged substantia nigra autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway,protect dopaminergic neurons,and treat PD.