中国药理学通报2023，Vol.39Issue(12)：2231-2239,9.DOI:10.12360/CPB202305082
ACT001通过STAT1/CIITA/MHC-Ⅱ通路发挥抗炎抗氧化活性治疗脓毒症引起的急性肺损伤
ACT001 exerts anti-inflammatory and antioxidative activity to alleviate sepsis-induced acute lung injury through STAT1/CIITA/MHC-Ⅱ pathway
摘要
Abstract
Aim This study aimed to assess the thera-peutic potential of ACT001,a micheliolide derivative,in the treatment of acute lung injury(ALI)induced by sepsis and investigate its pharmacological mechanisms.Methods At the animal level,an ALI model was es-tablished in mice through intraperitoneal injection of li-popolysaccharide(LPS).Subsequently,ACT001 was administered to the ALI-afflicted mice.The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate,lung inflammation,and pulmonary edema.At the cellular level,RAW264.7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001.The study examined inflammatory response and oxidative stress levels,and proteomics analysis was conducted to inves-tigate the underlying molecular mechanisms.Results At the animal level,ACT001 can improve the survival of mice with ALI,reduce lung inflammation,and re-duce the levels of inflammatory cytokines in serum.At the cellular level,ACT001 promotes the polarization of RAW264.7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-Ⅱ related pathways,inhibiting the production of NO and related inflammatory cyto-kines while increasing SOD content and scavenging ROS.Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity,mainly by inhibiting the STAT1/CIITA/MHC-Ⅱ pathway.ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.关键词
ACT001/LPS/脓毒症/急性肺损伤/MHC-Ⅱ/抗原处理与呈递Key words
ACT001/LPS/sepsis/acute lung injury/MHC-Ⅱ/antigen processing and presentation分类
医药卫生引用本文复制引用
盛磊,周杰诗,韩旭,李伊楠,刘慧娟,孙涛..ACT001通过STAT1/CIITA/MHC-Ⅱ通路发挥抗炎抗氧化活性治疗脓毒症引起的急性肺损伤[J].中国药理学通报,2023,39(12):2231-2239,9.基金项目
国家自然科学基金面上项目(No 82272934) （No 82272934）
国家级大学生创新创业训练计划(No 202210055112) （No 202210055112）
