Effect of Qingfei-Jiedu-Huatan Formula on severe pneumonia in rats via mTOR-regulated alveolar macrophage autophagy
10.3969/j.issn.1000-4718.2025.07.015
- VernacularTitle:基于mTOR调控肺泡巨噬细胞自噬研究清肺解毒化痰方对大鼠重症肺炎的影响
- Author:
Mingyan JIA
1
;
Yingjin LIANG
;
Kang ZHANG
;
Ya LI
;
Wenshuai JI
;
Chen DU
;
Xinxin KONG
;
Kai XIE
;
Pengzhen JING
;
Haifeng WANG
Author Information
1. 河南中医药大学第一附属医院呼吸科,河南中医药大学第一临床医学院,河南 郑州 450000;呼吸疾病中医药防治省部共建协同创新中心,河南 郑州 450046;河南中医药大学第一附属医院中药药理(呼吸)实验室,河南 郑州 450000
- Publication Type:Journal Article
- Keywords:
Qingfei-Jiedu-Huatan Formula;
severe pneumonia;
alveolar macrophages;
autophagy;
mammali-an target of rapamycin
- From:
Chinese Journal of Pathophysiology
2025;41(7):1383-1391
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.
