Protective effect of Xuebijing injection on sepsis-associated acute respiratory distress syndrome by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway
Objective To explore the protective mechanism of Xuebijing injection(referred to as Xuebijing)on sepsis-associated acute respiratory distress syndrome(ARDS).Methods ① Animal experiments:100 mice were randomly(random number)divided into 4 groups,including sham operation(Sham)group,cecal ligation and puncture(CLP)group,CLP+low-dose Xuebijing(L-XBJ)group,and CLP+high-dose Xuebijing(H-XBJ)group.The survival rate,lung histological changes,lung wet/dry(W/D)ratio,cell count and protein concentration in bronchoalveolar lavage fluids(BALF),inflammatory factors levels in serum,oxidative stress indicators,cell apoptosis,and key proteins of HIF-1α/p38 MAPK/NF-κB signaling pathway were measured.(2)Cell experiments:Mouse alveolar macrophages(MH-S)were cultured in vitro and divided into 6 groups,including control(Con)group,lipopolysaccharide(LPS)group,LPS+L-XBJ group,and LPS+H-XBJ group,LPS+H-XBJ+dimethyloxallyl glycine(DMOG,HIF-1α activator)group,LPS+H-XBJ+2-methoxyestradiol(2ME2,HIF-1α inhibitor)group.The effects of Xuebijing on inflammatory factors,oxidative stress,and cell apoptosis and their relationship with HIF-1α/p38 MAPK/NF-κB signaling pathway were detected.Results Xuebijing increased the survival rate of mice with sepsis-associated ARDS,relieved lung tissue damage[lung injury score:CLP group(8.778±0.588),CLP+L-XBJ group(5.833±0.310),and CLP+H-XBJ group(4.750±0.246)],alleviated lung W/D ratio,and decreased pneumonia cell infiltration and protein exudation(all P＜0.05).Additionally,Xuebijing treatment also diminished the expression of inflammatory factors(TNF-α,IL-1β,and IL-6),intracellular reactive oxygen species(ROS)accumulation,malondialdehyde(MDA)formation,superoxide dismutase(SOD)depletion,and cell apoptosis in LPS-induced MH-S cells and CLP-induced sepsis-associated ARDS mice(all P＜0.05).Furthermore,mechanistic investigation further clarified the effects of Xuebijing on inflammation,oxidative stress,and cell apoptosis through the HIF-1α/p38 MAPK/NF-κB signaling pathway.Conclusions Xuebijing can exert anti-inflammatory,anti-oxidative,and anti-apoptotic effects by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway,thereby conferring protection against sepsis-associated ARDS.
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