中国药理学通报2025，Vol.41Issue(5)：881-887,7.DOI:10.12360/CPB202411106
银杏叶提取物调控PI3K/Akt信号通路介导的细胞焦亡对大鼠脑缺血/再灌注神经元损伤的保护作用
The protective effect of ginkgo biloba extract on neuronal injury in rats with cerebral ischaemia reperfusion by regulating PI3K/Akt signaling pathway mediated pyroptosis
摘要
Abstract
Aim To investigate the effect of ginkgo bi-loba extract(GBE)interventional therapy on neuronal injury and pyroptosis in rats with cerebral ischaemia reperfusion(CIR)and its mechanism.Methods Male SD rats were randomly divided into sham opera-tion group(sham),CIR group,GBE low-dose group(GBE-L,25 mg·kg-1·d-1),and GBE high-dose group(GBE-H,100 mg·kg-1·d-1)and PI3K in-hibitor group(LY294002),with 24 rats in each group.The CIR rat model was established by suture method.After seven days of administration,the neuro-logical function damage was scored,and the water con-tent of the brain tissue was calculated;the pathological changes in the brain tissue of the rats in each group,the levels of inflammatory factors,the neuron pyropto-sis index,and the pyroptosis-related proteins(NL-RP3,ASC,caspase-1,GSDMD,IL-1 β,IL-18)and PI3K/Akt pathway protein expression were detected.Results The neurological function damage score,brain water content of the rats significantly increased(P＜0.01).The neurological structures showed marked pathological damage and infarct lesions.Serum TNF-α,IL-6,IL-1 β,IL-18 levels,the index of py-roptosis and the expressions of pyroptosis-related pro-teins(NLRP3,ASC,cleaved-caspase-1/pro-caspase-1,GSDMD-N/GSDMD,IL-1 β,IL-18)all significant-ly increased(P＜0.01),while p-PI3K/PI3K,p-Akt/Akt decreased in CIR group(P＜0.01).Different do-ses of GBE could reduce the neurological function dam-age score and brain tissue water content,improve neu-rological structure damage(P＜0.05 or P＜0.01),reduce serum TNF-α,IL-6,IL-1 β,the content of IL-18,the pyroptosis index,and the expression of pyrop-tosis-related proteins(P＜0.05 or P＜0.01),and in-crease p-PI3K/PI3K,p-Akt/Akt(P＜0.05 or P＜0.01).Compared with GBE-H group,LY294002 could reverse the protective effect of GBE on neuronal injury in CIR rats and induce neuronal pyroptosis.Conclusions GBE can improve neuronal injury in CIR rats,and its mechanism is related to promoting the activation of PI3K/Akt pathway and inhibiting neuronal pyroptosis.关键词
银杏叶提取物/脑缺血/再灌注/焦亡/神经元/PI3K/Akt信号通路Key words
ginkgo biloba extract/cerebral ischaemia/reperfusion/pyroptosis/neurons/PI3K/Akt signaling pathway引用本文复制引用
张昊,刘丽,刘丹..银杏叶提取物调控PI3K/Akt信号通路介导的细胞焦亡对大鼠脑缺血/再灌注神经元损伤的保护作用[J].中国药理学通报,2025,41(5):881-887,7.基金项目
国家自然科学基金资助项目(No 82000775) （No 82000775）
河南省医学科技攻关项目(No LHGJ20221058) （No LHGJ20221058）
