吴茱萸次碱可能通过PI3K/Akt/mTOR信号通路改善创伤性脑损伤  

Rutaecarpine May Improve Traumatic Brain Injury through PI3K/Akt/mTOR Pathway

作　　者：朱刚毅[1] 朱义通 陆兆丰[1] ZHU Gang-yi;ZHU Yi-tong;LU Zhao-feng(Kaiyuan Emergeney Department,the First Afiliated Hospital of Henan University ofScience and Technology,Zhengzhou 471000,China)

机构地区：[1]河南科技大学第一附属医院开元急诊科,郑州471000

出　　处：《中国临床神经科学》2024年第5期481-488,共8页Chinese Journal of Clinical Neurosciences

基　　金：河南省医学科技攻关计划项目(编号:SBGJ202102198);河南省医学教育研究项目(编号:Wjlx2021389)。

摘　　要：目的探讨吴茱萸次碱(Rut)对创伤性脑损伤(TBI)大鼠脑组织中磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白表达的影响。方法制备中度液压TBI大鼠模型,将TBI大鼠分为TBI组(给于0.9%氯化钠溶液),Rut低剂量(5 mg·kg^(-1))组,Rut中剂量(10mg·kg^(-1))组,Rut高剂量(20mg·kg^(-1))组,LY294002(Rut高剂量组+LY2940025mg·kg^(-1))组;对照组(大鼠仅颅骨钻孔,给于0.9%氯化钠溶液)。各组大鼠均n=15。评估各组大鼠神经功能、检测脑组织含水量和血脑屏障通透性,观察脑组织病理变化,检测大鼠神经元凋亡、氧化应激和炎症指标,Western blot检测蛋白表达水平。结果与对照组比较,TBI组半暗带脑组织损伤明显,Nissl体含量减少,mNSS、脑组织含水量、伊文思蓝渗出量、神经元凋亡率、MDA、TNF-α、IL-1β、Beclin-1、LC3-Ⅱ表达水平均显著升高(均P<0.05),p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR、P62表达均显著降低(均P<0.05);与TBI组比较,Rut低、中、高剂量组脑组织损伤改善,Nissl体形态和数量恢复,mNSS、脑组织含水量、伊文思蓝渗出量、神经元凋亡率、MDA、TNF-α、IL-1β水平、Beclin-1、LC3-Ⅱ表达均显著降低,p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR、P62表达均显著升高,且Rut各剂量组间呈剂量依赖性(P<0.05);LY294002逆转Rut对TBI大鼠脑组织损伤的改善作用。结论Rut可能通过激活PI3K/Akt/mTOR信号通路,减少神经元凋亡、氧化应激、炎症反应和自噬,改善TBI后脑损伤。Aim To investigate the impact of rutaecarpine(Rut)on the expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway related proteins in traumatic brain injury(TBI)rats.Methods SD rats were randomly separated into a control group,a TBI group,a low dose Rut group,a medium dose Rut group,a high dose Rut group,and a LY294002 group.A moderate hydraulic TBI rat model was prepared.The neurological function,the water content of brain tissue and blood-brain barrier permeability were evaluated for each group of rats.Pathological changes in brain tissue were observed.Neuronal apoptosis,oxidative stress and inflammation indicators of rats were detected,and Western blot was applied to detect protein expression.Results Compared with the control group,the brain tissue damage in the penumbra area of rats in the TBI group was obvious,the Nissl bodies content decreased,and mNSS score,brain tissue water content,evans blue exudation,neuronal apoptosis rate,the levels of MDA,TNF-α,IL-1β,the expression levels of Beclin-1 and LC3-Ⅱwere obviously increased(all P<0.05),the expression of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,and P62 were obviously reduced(all P<0.05).Compared with the TBI group,the brain tissue damage in the low,medium,and high dose Rut groups were improved,the morphology and quantity of Nissl bodies were restored,the mNSS score,brain tissue water content,evans blue exudation,neuronal apoptosis rate,the levels of MDA,TNF-α,IL-1β,and the expression levels of Beclin-1 and LC3-Ⅱwere obviously reduced,the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,and P62 were obviously increased,and there was dose dependence among the Rut groups(P<0.05).LY294002 reversed the improvement effect of Rut on brain tissue damage in the TBI rats.Conclusion Rut may reduce neuronal apoptosis,oxidative stress,inflammatory response,and autophagy by activating the PI3K/Akt/m TOR signaling pathway,thereby improving brain injury after TBI.

关 键 词：创伤性脑损伤 吴茱萸次碱 磷脂酰肌醇-3-激酶 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 

分 类 号：R651.15[医药卫生—外科学]