Effect of anti-inflammatory Tongfu formula on mtDNA-STING-NLRP3 signaling pathway in sepsis-induced acute lung injury rats
Huo Yan
Yue Di
Abstract：Objective To observe the effects of anti-inflammatory Tongfu formula on sepsis-induced acute lung injury(ALI)in rats and to explore its mechanism.Methods The 35 rats were randomly divided into normal group,model group,dexamethasone(DEX)group,traditional Chinese medicine(TCM)group and TCM +DEX group,with 7 rats in each group.The corresponding drugs were given by intragastric administration and the model was made.The contents of interleukin(IL)-6,IL-1β,IL-18,tumor necrosis factor-α(TNF-α)and serum macrophage count were detected by enzyme linked immunosorbent assay(ELISA).The expression levels of stimulator of interferon genes(STING),phosphorylated(P)-STING,NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC)mRNA and related proteins in lung tissues were detected by reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)and Western blot.The wet/dry ratio(W/D)of lung tissue was measured and the pathological changes of lung tissue were observed.The expression of macrophages in lung tissues was detected.Results Compared with the normal group,the indicators of other groups significantly increased.Compared with model group,the indicators in DEX group,TCM group and TCM +DEX group significantly decreased.The further comparison between the model group and the TCM + DEX group showed,lung tissue injury was improved,W/D value(4.77±0.29 vs.3.78±0.48)and macrophage count(13.39±2.06 vs.7.09±1.42)were decreased(P<0.05),IL-6(152.51±22.27 vs.58.92±13.53),IL-1β(126.19±10.02 vs.45.69±6.67),IL-18(59.12±6.31 vs.31.75±4.23)and TNF-α(126.57±8.25 vs.49.59±8.12)were decreased in the TCM +DEX group(P<0.01);The damage and release of mitochondrial DNA(mtDNA)in lung tissues,the expressions of P-STING(0.32±0.03 vs.0.16±0.03),STING mRNA(19.24±2.70 vs.0.32±0.16),NLRP3 mRNA(20.03±5.06 vs.1.20±0.04),ASC mRNA(16.96±4.31 vs.3.41±2.52)and related proteins in lung tissue were decreased in the TCM +DEX group(P<0.01).Conclusions Anti-inflammatory Tongfu formula may reduce inflammation in sepsis-induced acute lung injury rats by regulating mtDNA-STING-NLRP3 signaling pathway.
Keywords：Anti-inflammatory Tongfu formulaStimulator of interferon genes(STING)-NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathwaySepsisAcute lung injury(ALI)InflammationDexamethasoneMacrophages count
Publication Date：2024-04-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 323-329 )