中药新药与临床药理2026，Vol.37Issue(4)：598-606,9.DOI:10.19378/j.issn.1003-9783.2026.04.003
清热解毒扶正方药毒素清通过AMPK/PGC-1α信号通路促进线粒体生物发生从而改善细菌性肺炎的机制
The Heat-Clearing,Toxicity-Removing,and Healthy Qi-Reinforcing Formula Dusuqing Attenuates Bacterial Pneumonia via Promoting Mitochondrial Biogenesis Through the AMPK/PGC-1α Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism of Dusuqing(a formula with the functions of clearing heat,removing toxicity,and reinforcing healthy qi)in ameliorating bacterial pneumonia through regulating mitochondrial biogenesis via the AMPK/PGC-1α signaling pathway.Methods Fifty male C57BL/6J mice,aged 4-6 weeks,were randomly divided into five groups(n=10 per group):a blank control group,a model group,a high-dose Dusuqing group(15.6 g·kg-1),a low-dose Dusuqing group(7.8 g·kg-1),and a ceftriaxone group(0.195 g·kg-1).Drug interventions commenced 6-8 hours post-modeling.The high-and low-dose Dusuqing groups received oral gavage of Dusuqing solution at respective doses twice daily(morning and evening).The ceftriaxone group received intraperitoneal injection of ceftriaxone.The blank control and model groups received equivalent volumes of saline by gavage.General condition was monitored.Hematoxylin-eosin(HE)staining was used to observe pathological changes in lung tissue.The activities of mitochondrial respiratory chain complexes I and IV in lung tissue were measured by colorimetric assay.The content of reactive oxygen species(ROS)in lung tissue was detected using a commercial kit.Real-time quantitative polymerase chain reaction(RT-qPCR)was employed to assess mitochondrial DNA(mtDNA)copy number and the mRNA expression levels of AMPK,PGC-1α,nuclear respiratory factor 1(NRF1),mitochondrial transcription factor A(TFAM),NOD-like receptor protein 3(NLRP3),interleukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)in lung tissue.Western Blot analysis was performed to determine the p-AMPK/AMPK ratio and the protein expression levels of AMPK,PGC-1α,and NRF1 in lung tissue.Results Compared with the blank control group,the model group exhibited a significant decrease in body mass(P＜0.05),increased inflammatory infiltration in lung tissue,significantly elevated mRNA expression levels of inflammatory factors NLRP3,TNF-α,IL-1β,and IL-6(P＜0.05,P＜0.01),decreased mtDNA copy number(P＜0.05),reduced activities of mitochondrial respiratory chain complexes Ⅰ and Ⅳ(P＜0.05,P＜0.01),increased ROS levels(P＜0.01),significantly decreased mRNA expression levels of AMPK,PGC-1α,NRF1,and TFAM(all P＜0.01),and significantly reduced p-AMPK/AMPK ratio and protein expression levels of PGC-1α and NRF1(P＜0.05,P＜0.01).Compared with the model group,Dusuqing treatment led to increased body mass in mice(P＜0.05),markedly alleviated inflammatory injury in lung tissue,significantly decreased mRNA expression levels of NLRP3,TNF-α,IL-1β,and IL-6(P＜0.05,P＜0.01),increased mtDNA copy number(P＜0.01),elevated activities of mitochondrial respiratory chain complexes Ⅰ and Ⅳ(P＜0.05,P＜0.01),reduced ROS levels(P＜0.01),significantly increased mRNA expression levels of AMPK,PGC-1α,NRF1,and TFAM(P＜0.05,P＜0.01),and significantly elevated the p-AMPK/AMPK ratio and protein expression levels of PGC-1α and NRF1(P＜0.05,P＜0.01).Conclusion The Heat-Clearing,Toxicity-Removing,and Healthy Qi-Reinforcing Formula Dusuqing can ameliorate bacterial pneumonia,and its mechanism may be related to promoting mitochondrial biogenesis via modulating the AMPK/PGC-1α signaling pathway.关键词
毒素清/清热解毒扶正方/细菌性肺炎/线粒体生物发生/AMPK/PGC-1α信号通路/肺炎克雷伯杆菌/小鼠Key words
Dusuqing/Heat-Clearing,Toxicity-Removing,and Healthy Qi-Reinforcing Formula/bacterial pneumonia/mitochondrial biogenesis/AMPK/PGC-1α signaling pathway/klebsiella pneumoniae/mice分类
医药卫生引用本文复制引用
孙肖,梅雪,郑旭丹,徐菁菁,赵鹏,孙颖..清热解毒扶正方药毒素清通过AMPK/PGC-1α信号通路促进线粒体生物发生从而改善细菌性肺炎的机制[J].中药新药与临床药理,2026,37(4):598-606,9.基金项目
河南省自然科学基金资助项目(242300421294). （242300421294）
