Protective effect of large dose of ambroxol hydrochloride on lung ischemia-reperfusion inj ury in rats / 西安交通大学学报(医学版)

ABSTRACT

Objective To observe the effects of large-dose ambroxol hydrochloride on lung ischemia-reperfusion injury (LIRI)and discuss the protection of ambroxol hydrochloride on Toll-like receptor 4 (TLR4)/nuclear transcription factor-kappa B (NF-κB ) after lung ischemia-reperfusion injury in rats.Methods We randomly assigned 60 healthy SD rats into four groups (n=15 for each):control group,ambroxol hydrochloride group (0.75 g/L),ischemia-reperfusion group (I/R),and I/R+ambroxol hydrochloride group.The ambroxol hydrochloride group and I/R+ambroxol hydrochloride group were injected large dose of ambroxol hydrochloride by intravenous injection.The control group and the I/R group received normal saline.The effects of ambroxol hydrochloride on lung ischemia-reperfusion (LIR)-induced pathological changes and inflammatory cytokines release level were examined.DNA ends situ labeling assay (TUNEL)was used to detect the apoptosis of cells.NF-κBp6 5 was detected by immunohistochemistry.In addition,the TLR4 signaling pathway activation in lung tissues was detected by Western blot analysis.Results Compared with those in the control group,some hemorrhage and inflammation changes of lung tissues were observed;the W/D ratio,inflammatory cytokines,apoptosis of cells,NF-κBp6 5 and TLR4 signaling pathway protein expression in I/R group was obviously increased.Compared with I/R group,some mild hemorrhage and inflammation changes of lung tissues were observed;W/D ratio,inflammatory cytokines,apoptosis of cells, NF-κBp6 5 activity, and TLR4 signaling pathway expression were all decreased significantly in I/R+ambroxol hydrochloride group.Conclusion Large dose of ambroxol hydrochloride can protect rats with lung ischemia-reperfusion injury by downregulating TLR4 signaling pathway.