摘要
Objective To investigate the effect of H2S 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 （NariS） 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. NariS （0.78 mg/kg） as exogenous H2S donor and PPG （60 mg/kg） which can suppress endogenous H2S 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-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S 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.
Objective To investigate the effect of H2S 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 （NariS） 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. NariS （0.78 mg/kg） as exogenous H2S donor and PPG （60 mg/kg） which can suppress endogenous H2S 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-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S 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.
基金
supported by the Military Health Care Foundation during the 12th Five-year Plan Period(11BZ21)
the Military Scientific Research Foundation during the 12th Five-year Plan Period(BWS12J051)
