肺灌注抗肿瘤坏死因子抗体对体外循环肺超微结构的影响

Intra-pulmonary arterial antitumor necrosis factor-α antibody effect on ultra-structure of lung following cardiopulmo-nary bypass

目的探讨肺动脉灌注抗肿瘤坏死因子-α抗体（TNF．仅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-αAb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-αmRNA、Bcl-2、Bax表达和Bcl-2／Bax及凋亡指数变化情况。结果TNF-αAb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-αAb组肺组织病理形态学改变较轻。结论肺动脉灌注TNF-αAb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。

Objective 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 ran- domly 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 mi-nute. Pulmonary arterial perfusion was given to the group I instead. Blood TNF-α and neutrophils count from right and left a-trium and oxygenation index in the four groups were determined perioperatively. Lung water content, TNF-α messenger 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 ex-pression 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.