Mechanism of lentinan regulating TGF-β/Smad2 signaling pathway on the inflammatory response in tuberculosis-infected rats

ZHANG Ying; LYU Bing; GUO Chunhui

doi:10.3969/j.issn.1007-8134.2025.02.009

Abstract：Objective The aim of this study was to investigate the impact of lentinan on the inflammatory response in rats with tuberculosis and to preliminary explore its underlying mechanism of action.Methods A tuberculosis rat model was established by tail vein injection of Mycobacterium tuberculosis.Successfully modeled rats were randomly divided into five groups:a model group,a rifampicin group,and low(25 mg/kg),medium(50 mg/kg),and high(100 mg/kg)lentinan dose groups,with 10 rats in each group.Additionally,10 SD male rats were selected as the control group.After 4 weeks of drug treatment,a blood analysis system was used to detect the number of inflammatory cells in the bronchoalveolar lavage fluid(BALF)of rats in each group.Histopathological damage to lung tissue was observed via hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of pro-inflammatory cytokines[tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,IL-6],and anti-inflammatory cytokine IL-10 in lung tissue.Quantitative real-time polymerase chain reactionq(qRT-PCR)and Western Blot were employed to detect mRNA and protein expression levels of proteins related to the transforming growth factor(TGF-β)/mothers against decapentaplegic homolog 2(Drosophila)(Smad2)signaling pathway.Results Compared with the control group,the model group exhibited a significant increase in the number of inflammatory cells in BALF(P＜0.05),along with markedly enhanced pathological damage and inflammatory cell infiltration in lung tissue.Levels of pro-inflammatory cytokines TNF-α,IL-1 β,and IL-6 were significantly elevated(P＜0.05),while IL-10 levels were notably decreased(P＜0.05).Additionally,messenger ribonucleic acid(mRNA)and protein expression levels of proteins related to the TGF-β/Smad2 signaling pathway were significantly increased(P＜0.05).In comparison to the model group,the rifampicin group and the low,medium,and high lentinan dose groups showed a significant reduction in the number of inflammatory cells in BALF(P＜0.05),with alleviated pathological damage and inflammatory cell infiltration in lung tissue.Levels of pro-inflammatory cytokines TNF-α,IL-1 β,and IL-6 were significantly decreased(P＜0.05),while IL-10 levels were notably increased(P＜0.05).The expression levels of TGF-β,Smad2 mRNA,and TGF-β,p-Smad2 protein were significantly decreased(P＜0.05),with the high-dose lentinan exhibiting the best effect.Furthermore,a dose-dependent relationship was observed among the lentinan groups.Conclusion Lentinan can attenuate the inflammatory response in a rat model of tuberculosis,and its mechanism of action may be related to lentinan's inhibition of the activation of the TGF-β/Smad2 signaling pathway.