摘要目的 探讨肺动脉灌注抗肿瘤坏死因子-α抗体(TNF-α Ab)对体外循环(CPB)肺损伤组织超微结构的影响.方法 选取新西兰白兔40只,数字表法随机分为CPB+单纯肺动脉灌注液组、CPB+肺动脉灌注TNF-α Ab组、单纯CPB组和单纯开胸组.测定各组围CPB期血浆TNF-α、中性粒细胞含量及氧合指数；取肺组织样本,电镜观察其超微结构,并检测肺组织含水量、TNF-α mRNA、Bcl-2、Bax表达和Bcl-2/Bax及凋亡指数变化情况.结果 TNF-α Ab可明显抑制肺源性TNF-α表达和释放,减少CPB期间中性粒细胞在肺内的聚集,降低肺含水量,提高氧合指数,并减少肺组织细胞凋亡发生,降低肺泡上皮细胞Bax蛋白表达,减轻Bcl-2蛋白表达下降,且TNF-α Ab组肺组织病理形态学改变较轻.结论 肺动脉灌注TNF-α Ab能明显减轻炎性肺损伤及由Bcl-2/Bax凋亡途径引起的肺组织超微结构损伤.

abstractsObjective To study the effect of intra-pulmonary arterial anti-tumor necrosis factor-α antibody(TNF-α Ab) on ultra-structure of lung after cardiopulmonary bypass (CPB).Methods Forty New Zealand rabbits were selected and randomly divided into four groups:group Ⅰ-Ⅲ underwent CPB; group Ⅳ only received open chest operation.In the group Ⅱ,rabbit TNF-α Ab(27 ng/kg) was dropped into the pulmonary artery when the aorta was clamped and CPB continued 30 minute.Pulmonary arterial perfusion was given to the group I instead.Blood TNF-α and neutrophils count from right and left atrium and oxygenation index in the four groups were determined perioperatively.Lung water content,TNF-αmessenger RNA,Bcl-2 protein,Bax protein,Bcl-2/Bax,apoptosis index and pathomorphological change were measured in the lung tissues.Results TNF-α Ab can restrain leukocyte accumulation and reduce releasing of TNF-α in the lung and improve oxygenation index.Moreover,TNF-α Ab can reduce the expression of Bax on alveolar epithelial cells and alleviate the decreasing of the expression of Bcl-2.It can also reduce the occurrence of apoptosis and attenuate pathomorphological changes in the lung tissue.Conclusion Intra-pulmonary arterial antitumor necrosis factor-α antibody markedly lessens the injury of inflammatory reaction and ultra-structure of lung after CPB via Bcl-2/Bax pathway.