青蒿素改善脓毒症小鼠急性肺损伤的剂量相关性研究OA

Objective:To investigate the protective effects and dose-dependent relationship of different doses of artemisinin(ART)on acute lung injury in septic mice induced by Gram-positive(G+)and Gram-negative(G-)bacteria.Methods:A total of 90 C57BL/6 mice were randomly divided into the Staphylococcus aureus(G+)and Escherichia coli(G-)groups.Each group included the sham surgery,G+/G-sepsis model,sepsis+2%dimethyl sulfoxide(DMSO)control,and sepsis+different doses of ART(5,10,15,20,25 mg/kg)subgroups.Pro-inflammatory cytokines[tumor necrosis factor-α(TNF-α),interleukin 6(IL-6)]and anti-inflammatory cytokine interleukin 10(IL-10)levels in serum and bronchoalveolar lavage fluid(BALF),lung wet/dry weight ratio(W/D),and H&E staining scores were measured in each experimental group.Results:ART treatment groups dem-onstrated significant dose-dependent protective effects with increasing dosages(5‒25 mg/kg):(1)Inflammatory cytokine levels showed dose-dependent improvement,with the 25 mg/kg dose group significantly reducing TNF-α and IL-6 levels while increas-ing IL-10 level in mice BALF(P<0.05);(2)Pulmonary edema gradually improved with increasing dosages,with high-dose groups(20,25 mg/kg)significantly reducing lung tissue W/D ratios(P<0.05);(3)Pathological damage showed dose-dependent alleviation,most siginficantly in the 25 mg/kg group,characterized by reduced inflammatory cell infiltration and improved alveolar structure.Among all dosage groups,25 mg/kg demonstrated the optimal protective effect.Conclusion:ART ex-hibits significant dose-dependent protective effects against sepsis-induced acute lung injury,with 25 mg/kg being the optimal therapeu-tic dose.The mechanism may be related to dose-dependent inhibition of pro-inflammatory cytokine release,promotion of anti-inflammatory cytokine expression,and improvement of pulmonary edema.These findings provide important evidence for the clinical application of ART in sepsis-related acute lung injury.