基于PI3K/AKT/mTOR通路探讨大黄素调控自噬对脓毒症小鼠心肌损伤保护作用  

Protective effect of emodin on the regulation of autophagy in mice with sepsis-induced myocardial injury based on the PI3K/AKT/mTOR pathway

作　　者：王萌 李华 王帝[1] 邓健超 WANG Meng;LI Hua;WANG Di;DENG Jianchao(The Second Clinical College of Medicine,Henan University of Chinese Medicine,Zhengzhou 450002,China;Henan Province Hospital of Traditional Chinese Medicine/The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450002,China)

机构地区：[1]河南中医药大学第二临床医学院,郑州450002 [2]河南省中医院/河南中医药大学第二附属医院,郑州450002

出　　处：《吉林中医药》2025年第3期348-352,共5页Jilin Journal of Chinese Medicine

基　　金：河南省中医药科学研究专项课题(2024ZY2063);河南省高等学校重点科研项目计划(21A320009);北京协和医学基金-睿E(睿意)急诊医学研究专项基金(22222012006)。

摘　　要：目的基于PI3K/AKT/mTOR自噬信号通路探讨大黄素干预脓毒症心肌损伤的机制及作用靶点。方法将50只BALB/c雄性小鼠随机分为空白组、模型(LPS)组、空白+大黄素组、LPS+大黄素组、3-MA+大黄素+LPS组,超声心电图检测小鼠心功能指标;全自动生化分析仪检测血清心肌酶;HE染色观察心肌组织形态学改变;ELISA法检测心肌组织IL-6、TNF-α、MDA、SOD含量;Western blot检测自噬标志蛋白(LC3-Ⅱ/Ⅰ、Beclin-1),PI3K、AKT、mTOR各自磷酸化水平。结果LPS组小鼠心功能降低,心肌酶升高,心肌结构紊乱,促炎因子水平升高,SOD活性降低,MDA水平升高,心脏自噬明显被抑制。大黄素干预后,心功能明显改善,心肌紊乱及炎症减轻,SOD活性升高,MDA水平降低,自噬激活,PI3K、AKT、mTOR的磷酸化水平明显降低;应用自噬抑制剂3-MA后,心肌损伤程度及炎症加重,SOD活性降低,MDA水平升高,自噬抑制,PI3K、AKT、mTOR的磷酸化水平明显升高。结论大黄素可减轻LPS诱导的脓毒症小鼠心肌病理损伤、氧化应激和炎症反应,增强自噬,其机制与抑制PI3K/AKT/mTOR信号通路激活有关。Objective To investigate the mechanism and targets of emodin intervention in sepsis-induced myocardial injury based on the PI3K/AKT/mTOR autophagy signaling pathway.Methods Fifty BALB/c male mice were randomly divided into 5 groups:a blank group,a model(LPS)group,a blank+emodin group,an LPS+emodin group,and a 3-MA+emodin+LPS group.The cardiac function indicators of the mice were detected by ultrasound electrocardiogram.Their serum myocardial enzymes were detected by automatic biochemical analyzer.The morphological changes in myocardial tissue were observed by HE staining.The levels of IL-6,TNF-α,MDA,and SOD in myocardial tissue were detected by ELISA.The phosphorylation levels of autophagy marker proteins(LC3-II/I,Beclin-1)and PI3K,AKT and mTOR were detected by Western blot.Results In the LPS group,the cardiac function was decreased,the cardiac enzymes were increased,the myocardial structure was disordered,the levels of pro-inflammatory factors were increased,the activity of SOD was decreased,the level of MDA was increased,and the cardiac autophagy was significantly inhibited.After the emodin intervention,their cardiac function was significantly improved,the myocardial disorders and inflammation were reduced,the SOD activity was increased,the MDA level was reduced,the autophagy was activated,and the phosphorylation levels of PI3K,AKT,mTOR were significantly reduced.After the application of autophagy inhibitor 3-MA,the degree of myocardial injury and inflammation was worsened,the SOD activity was decreased,the MDA level was increased,the autophagy was inhibited,and the phosphorylation levels of PI3K,AKT,and mTOR were significantly increased.Conclusion Emodin can alleviate myocardial pathological injury,oxidative stress and inflammatory responses and enhance autophagy in LPS-induced sepsis mice,whose mechanism is related to the inhibition of PI3K/AKT/mTOR signaling pathway activation.

关 键 词：大黄素 脓毒症心肌损伤 PI3K/AKT/mTOR信号通路 自噬 

分 类 号：R542.2[医药卫生—心血管疾病]