Study Of The Effect Of Tanshinone ⅡA On Acute Lung Injury In Sepsis Based On Neutrophil Extracellular Traps

Objective: To study the effect of tanshinone ⅡA(TanⅡA)on acute lung injury(ALI)in septic mice based on neutrophil extracellular traps(NETs)and to explore its possible mechanism.Methods: 24 healthy male SPF C57BL/6J mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups according to the random number table method:(1)normal group(Nor group),(2)lipopolysaccharide group(LPS group,intraperitoneal injection of LPS 10 mg/kg to establish sepsis model),(3)Tanshinone ⅡA group(LPS+TanⅡA group,30 mg/kg Tan IIA was injected intraperitoneally 30 min before LPS injection),(4)LY294002 group(LPS+LY294002 group,30 mg/kg LY294002 was injected intraperitoneally 30 min before LPS injection),and with 6 mice in each group.At 12 h after modeling,the lung tissues were collected,lung coefficients were calculated,and pathological changes of lung tissue were observed by HE.ELISA was used to detect the levels of inflammatory factors IL-1β and IL-10 and the NETs markers MPO-DNA complex and citrolinated histone H3(Cit H3)in lung tissue.Western blot was applied to detect the phosphorylation of PI3K/Akt signaling pathway.Results: Compared with the Nor group,the LPS group had an increased lung coefficient,significantly damaged lung tissue,increased levels of IL-1β(P<0.05)and decreased levels of IL-10(P<0.05),and elevated MPO-DNA complex and Cit H3 levels(P<0.05)as well as the levels of p-PI3 K and p-Akt levels(P<0.05).While,the above conditions were much better in the LPS+TanⅡA group and the LPS+LY294002 group than the LPS group,with decreased lung coefficients,alleviated lung injury by HE staining and lung injury scores,decreased levels of IL-1β and increased levels of IL-10 in lung tissue(P<0.05),reduced levels of MPO-DNA complex and Cit H3(P<0.05)and p-PI3 K and p-Akt(P<0.05).Conclusion: Tanshinone ⅡA may exert a protective effect against ALI in sepsis by regulating the level of NETs through inhibition of the activation of PI3K/Akt signaling pathway to attenuate the inflammatory response.