中国中药杂志2025，Vol.50Issue(14)：3857-3867,11.DOI:10.19540/j.cnki.cjcmm.20250416.501
基于IRE1α/ASK1/JNK通路探讨补阳还五汤对缺血性脑卒中大鼠神经功能恢复作用及机制
Effect and mechanism of Buyang Huanwu Decoction in improving neurological function in ischemic stroke rats based on IRE1α/ASK1/JNK pathway
摘要
Abstract
This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK)pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI).SPF-grade male sprague-dawley(SD)rats were randomly divided into Sham group,model group,Buyang Huanwu Decoction group,and edaravone group.Except for the Sham group,the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R)model.After treatment,neurological function was assessed using the Zea Longa scoring system.Gait analysis was used to detect the motor function.Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC)staining.Nissl staining was used to observe the structure of neuronal cells.Western blot and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect IRE1α,ASK1,JNK,B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax),and Caspase-3 in the brain tissue.Immunohistochemistry was used to detect the positive expression of IRE1α,ASK1,and JNK.Immunofluorescence was used to detect the fluorescence expression levels of Bax,Bcl-2,and Caspase-3.The results showed that compared with the Sham group,the model group exhibited increased neurological scores(P＜0.01),increased ratio of ground contact area and strength in both forelimbs(P＜0.01),enlarged relative infarct area of brain tissue(P＜0.05),and a reduced number of Nissl staining-positive cells(P＜0.01).The protein and mRNA expression levels of IRE1α,ASK1,JNK,Bax,and Caspase-3 in brain tissue were significantly elevated,while those of Bcl-2 were decreased(P＜0.05).Compared with the model group,both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P＜0.05),decreased ratio of ground contact area and strength in both forelimbs(P＜0.05),smaller relative infarct area(P＜0.05),alleviated neuronal damage,and increased number of Nissl staining-positive cells(P＜0.05).The expression levels of IRE1α,ASK1,JNK,Bax,and Caspase-3 protein and mRNA in brain tissue were significantly reduced,while those of Bcl-2 were significantly increased(P＜0.05).The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats,and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.关键词
脑缺血/再灌注损伤/IRE1α/ASK1/JNK通路/补阳还五汤/内质网应激Key words
cerebral ischemia/reperfusion injury/IRE1α/ASK1/JNK pathway/Buyang Huanwu Decoction/endoplasmic reticulum stress引用本文复制引用
张馨蓉,王天朗,张家豪,金璐,王建波,薛亚楠,曲怡..基于IRE1α/ASK1/JNK通路探讨补阳还五汤对缺血性脑卒中大鼠神经功能恢复作用及机制[J].中国中药杂志,2025,50(14):3857-3867,11.基金项目
辽宁省科学技术青苗项目(2023-MSLH-178) （2023-MSLH-178）
辽宁省教育厅高校基本科研项目(面上项目)(LJKMZ20221315) （面上项目）
