摘要
目的基于网络药理学和体内实验探究抗感合剂干预急性肺损伤(ALI)的分子机制。方法应用网络药理学预测抗感合剂(Kanggan mixture,KGM)干预ALI的靶基因和主要通路;脂多糖(LPS)诱导ALI大鼠模型,运用micro-CT评估活体大鼠体内肺损伤程度,实验验证KGM对ALI大鼠的干预作用机制。结果结果显示从KGM中共筛选出190种化学成分、预测出KGM干预ALI的579个潜在靶点,通路204条。抗感合剂中的核心成分槲皮素、木犀草素、山柰酚、白桦脂醇、羽扇豆酮,通过作用于TP53、AKT1、SRC、EP300和STAT3等靶点,调控FoxO信号通路、TNF信号通路、PI3K-Akt信号通路、MAPK信号通路等,展现出抗病毒、抗炎及免疫调节的能力,对急性肺损伤具有干预作用。micro-CT结果提示,抗感合剂可改善ALI大鼠肺纹理增强以及肺损伤,且(吸气相-呼气相)末端肺体积上升。HE和W/D比值结果表明,KGM可改善肺组织损伤,降低肺组织湿/干重比(P<0.01),血细胞分析结果显示抗感合剂可使ALI大鼠血液WBC(白细胞计数)和N%(中性粒细胞百分比)减少(P<0.01),淋巴细胞增加(P<0.05)。实时定量PCR、WES和免疫组化结果提示,KGM可减少ALI大鼠肺组织TP53、AKT1、SRC、EP300和STAT3 mRNA表达量、蛋白分布和蛋白表达量(P<0.05)。结论抗感合剂对急性肺损伤有一定干预作用,主要通过核心靶点STAT3、EP300、SRC、AKT1、TP53实现。
Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.
作者
黄赫
管仲莹
王德成
朱竟赫
靖博宇
张瑜
刘小虎
关铁发
范英兰
甘雨
赵磊
HUANG He;GUAN Zhongying;WANG Decheng;ZHU Jinghe;JING Boyu;ZHANG Yu;LIU Xiaohu;GUAN Tiefa;FAN Yinglan;GAN Yu;ZHAO Lei(Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China;Liaoning Institute of Traditional Chinese Medicine,Shenyang 110034,China)
出处
《世界科学技术-中医药现代化》
北大核心
2025年第5期1447-1460,共14页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
辽宁省科学技术厅联合基金面上项目(2023-MSLH-156):基于“卫气营血”理论探讨宣白承气汤调控STING/IRF3/IFNβ轴驱动NLRP3治疗急性肺损伤的分子机制研究,负责人:黄赫
辽宁省教育厅面上项目(LJKMZ20221329):基于甘草纳米“舟楫”递药模式的雷公藤甘草配伍减毒增效作用机制的研究,负责人:靖博宇
辽宁中医药大学附属第二医院育苗项目(2023-LZYY-1-27):基于炎症小体NLRP3通路的抗感合剂干预急性肺损伤分子机制研究,负责人:黄赫。
