原位肝移植大鼠供肝冷缺血时间对受体肺损伤的影响

Effect of cold-ischemia time in the graft on acute lung injury after orthotopic liver transplantation in rats

Objective To study the mechanism and effect of pulmonary insufficiency induced by nuclear factor-κB (NF-κB) activation and inflammatory response on the extended cold-preserved graft after orthotopic liver transplantation (OLT). Methods OLT was performed with varying time periods of cold ischemia (6 ,18 and 24 hr in University Wisconsin solution at 4℃). We determined the time course of NF- κB activation and expression of neutrophil chemoattractant: cytokine-inducible neutrophil chemoattractant (CINC) and macrophage inflammatory protein (MIP-2) within 6h after reperfusion. Pulmonary leukocyte accumulation and pulmonary microvascular permeability were assessed after 6h reperfusion. Results The activation of NF- κB in the lung of 18h and 24h cold-ischemia group within 1h after reperfusion, but strongly activated at 2h after reperfusion compared with the 6h groups. The accumulation of neutrophil in the lung significantly increased since 2h after reperfusion, which was synchronized with the common situation of the recipients after transplantation. Prolonged cold-preservation did not affect the time course for neutrophil accumulation. NF- κB activation preceded the expression of CINC and MIP-2 in the lung, which was significantly increased with prolonged cold preservation. In prolonged cold preserved graft, prominent elevated NF- κB activation occurred at 1h, consistent with greatly increased intrapulmonary neutrophil chemoattractant response at 2h after reperfusion. Conclution NF- κB activation correlated with the expression of CINC and MIP-2 in vivo in OLT rats. Extended cold preservation of the graft might up-regulate CINC and MIP-2 expression in the lung, most probably through elevated NF- κB activation, and might contribute to neutrophil inflammation in the lung after reperfusion.

Objective To study the mechanism and effect of pulmonary insufficiency induced by nuclear factor- κB （NF -κB） activation and inflammatory response on the extended cold- preserved graft after orthotopic liver transplantation （OLT）. Methods OLT was performed with varying time periods of cold isehemia （6 , 18 and 24 hr in University Wiseousiu solution at 4℃ ）. We determined the time course of NF - κB activation and expression of neutrophil chemoattractant ： cytokine -inducible neutrophil ehemoattractant （CINC） and macrophage inflammatory protein （MIP- 2） within 6h after repeffusiou. Pulmonary leukocyte accumulation and palmonary mierovaseular permeability were assessed after 6h reperfusion. Results The activation of NF - κB in the lung of 18h and 24h cold - isehemia group within lh after reperfusion, but strongly activated at 2h after reperfusion compared with the 6h groups. The accumulation of nentrophil in the lung significantly increased since 2h after repeffusion, which was synchronized with the common situation of the recipients after transplantation. Prolonged cold - preservation did not affect the time course for neutrophil aecumulation. NF- κB activation preceded the expression of CINC and MIP-2 in the lung, which was siguifieantly increased with prolonged cold preservation. In prolonged cold preserved graft, prominent elevated NF - κB aetivation occurred at 1h, consistent with greatly increased intrapulmonary neutrophil ehemoattraetant response at 2h after reperfusion. Conclution NF- κB activation correlated with the expression of CINC and MIP-2 in vivo in OLT rats. Extended cold preservation of the graft might up -regulate CINC and MIP-2 expression in the hmg, most probably through elevated NF- κB activation, and might contribute to neutrophil inflammation in the lung ＂after reperfusion.