改良兔体外循环急性肺损伤模型的建立

Establishment of a modified rabbit model of acute lung injury induced by cardiopulmonary bypass

目的探讨改良经主动脉、右心房插管,自体血预充的兔体外循环(CPB)急性肺损伤模型,及外周血肿瘤坏死因子α水平变化。方法随机选择10只健康成年雄性新西兰兔建立体外循环模型。待心脏复跳稳定,终止体外循环后,兔存活4 h即判定为模型制作成功。监测生命体征,分别记录在麻醉后(T_1)、在体外循环转流前(T_2),阻断主肺动脉后15 min时(T_3),主肺动脉的重新开放灌流后(T_4),体外循环结束后1 h(T_5)、4 h(T_6)的生命体征值,与T2、T_4、T_6时刻采集动脉血进行血气分析,采用酶联免疫吸附(ELISA)法检测T2、T_5、T_6时刻外周血中肿瘤坏死因子α(TNF-α)水平。结果通过对10只兔的实验,成功改良了兔CPB急性肺损伤模型。术中平均动脉压维持55 mm Hg以上,体外转流前后红细胞压积显著下降(T230.18±2.88%,T_417.73±1.95%,P<0.05),血浆乳酸Lac浓度逐步升高,开放主肺动脉时明显增加(T23.65±1.13 mmol/L,T_49.36±1.28 mmol/L,P<0.05)。T_6氧合指数(PaO_2/FiO_2)比T2显著下降(T2468.36±56.28 mm Hg,T_6281.64±55.76 mm Hg,P<0.05),血清中TNF-α水平显著升高(P<0.05),肺间质水肿显著,炎性细胞浸润增加。结论本实验改良的兔CPB急性肺损伤模型稳定可靠,可为研究体外循环引起的急性肺损伤提供稳定可靠的研究基础。

Objective To establish an modified rabbit model of the acute lung injury induced by cardiopulmonary bypass （CPB） with ascending aorta and right atrium catheterization and detect the changes in serum tumor necrosis factor-α（TNF-α） level after modeling. Methods Ten healthy adult male New Zealand rabbits were randomly selected to establish CPB models. The model establishment was deemed successful if the rabbits survived for over 4 h with stable heart beat after termination of CPB. The vital signs of the rabbits were recorded after anesthesia （T1）, before CPB （T2）, at 15 after blocking the ascending aorta and pulmonary artery （T3）, immediately after re-opening of the ascending aorta and pulmonary artery （T4）, and at 1 （T5） and 4 （T6） after CPB. Arterial blood gas （ABG） was monitored at T2, T4 and T6 and the serum levels of TNF-α were also detected with ELISA. Results Nine rabbit models of CPB with acute lung injury were successfully established. During the operation, the MAP was maintained at a level above 55 mmHg, HCT significantly decreased from （30.18 ＆#177; 2.88）%at T2 to （17.73 ＆#177; 1.95）%at T4 （P〈0.05）, and plasma lactate level increased significantly from 3.65 ＆#177; 1.13 mmol/L at T2 to 9.36 ＆#177; 1.28 mmol/L at T4 （P〈0.05）. The oxygenation index （PaO2/FiO2） at T6 was significantly lower than that at T2 （281.64 ＆#177; 55.76 vs 468.36 ＆#177; 56.28 mmHg, P〈0.05）. The serum levels of TNF-α were significantly increased （P〈0.05） and obvious lung interstitial edema and inflammatory cell infiltration occurred after CPB establishment. Conclusion The modified rabbit model of CPB with acute lung injury is stable and reliable and can be used for studying acute lung injury induced by CPB.