H2SProtectingagainstLungInjuryfollowingLimbIschemia-reperfusionbyAlleviatingInflammationandWaterTransportAbnormalityinRats

Objective To investigate the effect of H2 S on lower limb ischemia-reperfusion(LIR) induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide(NaHS) group and IR+ DL-propargylglycine(PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS(0.78 mg/kg) as exogenous H2 S donor and PPG(60 mg/kg) which can suppress endogenous H2 S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1(AQP1), aquaporin-5(AQP5) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4(TLR4), myeloid differentiation primary-response gene 88(MyD88) and p-NF-κB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NaHS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-κB pathway, but PPG adjusted AQP1/AQP5 and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2 S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2 S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.