中国临床药理学与治疗学2025，Vol.30Issue(8)：1037-1048,12.DOI:10.12092/j.issn.1009-2501.2025.08.004
基于自噬流及CXCL12/CXCR4轴研究天麻钩藤饮对肝阳上亢证脑缺血再灌注大鼠模型的神经保护作用及机制
Study on the neuroprotective effect and mechanism of Tianma Gouteng Decoction on combining rat model of Hyperactivity of Liver Yang and MCAO based on autophagic flux and CXCL12/CXCR4 axis
摘要
Abstract
AIM:To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction(TMGTD).METHODS:SD rats were divided into sham,model,TMGTD high/medium/low-dose(20.52/10.26/5.13 g·kg-1·d-1),and Nimodipine(30 mg·kg-1·d-1)groups.A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was es-tablished using Fuzi Decoction(2 g·kg-1·d-1)and thread-occlusion.After 21 days of Fuzi decoction pretreatment,rats received daily drug administra-tion for 12 days.Syndrome indicators(irritability,24-hour water intake,24-hour urine volume,facial temperature)were recorded,plasma NE,E,cAMP,and cGMP were measured by ELISA,neurological function was assessed using Zea Longa and mNSS methods,brain histopathology was evaluated by HE staining,protein expression of soluble/insoluble p62 and LC3B was detected by Western blot,au-tophagy-related genes were analyzed by PCR array,additionally,mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot.RESULTS:Compared to the sham group,the model group showed increased irritability,24-hours water intake,24-hours urine volume,facial temper-ature,and level of NE,E,cGMP(P＜0.01),neurologi-cal scores(P＜0.01),LC3B-Ⅱ,insoluble p62,CXCR4,CXCL12 expression(P＜0.01),but decreased soluble p62(P＜0.01).TMGTD groups exhibited reduced irri-tability,water intake,urine volume,facial tempera-ture,NE,E,cGMP(P＜0.05,P＜0.01),neurological scores(P＜0.05,P＜0.01),p62 expression(P＜0.01),alongside increased LC3B-Ⅱ(P＜0.01)and improved cortical pathology.TMGD also reversed dysregulat-ed autophagy-apoptosis genes(CXCR4,Lamp1,Tgfb1,APP,Rab24)and reduced CXCR4,CXCL12 ex-pression(P＜0.01).CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model,autophagy genes were activated but flux was impaired,and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.关键词
天麻钩藤饮/缺血性脑卒中/肝阳上亢证/自噬流/PCR阵列/CXCL12/CXCR4轴Key words
Tianma Gouteng Decoction/ischemic stroke/hyperactivity of liver Yang/autophagic flux/PCR array/CXCL12/CXCR4 axis分类
医药卫生引用本文复制引用
王晓丽,邵静,张薇,田萍,张雪侠,刘长河,李开言,杨丹,郭晓燕..基于自噬流及CXCL12/CXCR4轴研究天麻钩藤饮对肝阳上亢证脑缺血再灌注大鼠模型的神经保护作用及机制[J].中国临床药理学与治疗学,2025,30(8):1037-1048,12.基金项目
河南省自然科学基金青年项目(222300420200) （222300420200）
国家自然科学基金项目(81641147) （81641147）
河南省中医药科学研究专项(2023ZY3019) （2023ZY3019）
河南省基本科研业务费(2204972,2304019) （2204972,2304019）
