Effects and mechanism of formononetin on acute lung injury and immune function in septic rats
Objective To investigate the effects of formononetin(Formo)on acute lung injury and immuno-logic function in septic rats by regulating the high mobility group protein B1(HMGB1)/receptor for dvanced glyca-tion end products(RAGE)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Sepsis rats were estab-lished by cecal ligation and puncture.After modeling,the rats were randomly grouped into sepsis group,Formo low dose(Formo L)group(15 mg/kg Formo),Formo medium dose(Formo M)group(30 mg/kg Formo),Formo high dose(Formo H)group(60 mg/kg Formo),Formo H+recombinant HMGB1 protein(rHMGB1)group(60 mg/kg Formo+8 μg/kg rHMGBl),and only incisions were made,rats that did not undergo cecal ligation or puncture were in the sham surgery group.After the intervention,the wet to dry ratio(W/D)of rat lung tissue was detected;abdom-inal blood was collected,flow cytometry and ELISA were applied to detect immune function and levels of interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in rats;HE was applied to detect pathological changes in the upper lobe of the right lung;Western blot was applied to detect protein expression related to the HMGB1/RAGE/NF-κB signaling pathway in lung tissue.Results Compared with the control group,the pathological damage to lung tissue in the sepsis group was severe,CD4+and CD4+/CD8+were obviously decreased,the levels of TNF-α,IL-1 β,IL-6,pathological injury score,W/D,CD8+,and the expression of HMGB1,RAGE p-NF-κB p65/NF-κB p65 were obviously increased(P＜0.05);compared with the sepsis group,the pathological damage in the Formo L,Formo M,and Formo H groups improved,CD4+and CD4+/CD8+were obviously increased,the levels of TNF-α,IL-1β,IL-6,pathological injury score,W/D,CD8+,and the expression of HMGB1,RAGE,p-NF-KB p65/NF-KB p65 were obvi-ously reduced,with differences among groups(P＜0.05);compared with the Formo H group,the pathological dam-age in the Formo H+rHMGB1 group worsened,CD4+and CD4+/CD8+were obviously decreased,the levels of TNF-α,IL-1β,IL-6,pathological injury score,W/D,CD8+,and the expression of HMGB1 RAGE p-NF-KB p65/NF-κB p65 were obviously increased(P＜0.05).Conclusion Formo may reduce acute lung injury and improves im-mune function in septic rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.
FormononetinSepsisAcute lung injuryHMGB1/RAGE/NF-κB signaling pathwayImmunologic function
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