大鼠体外循环后肺损伤的实验研究

Lung injury after cardiopulmonary bypass in rats

目的研究大鼠体外循环(cardiopulmonary bypass,CPB)后肺脏损伤及其相关机制。方法 24只雄性SD大鼠随机均分成两组:伪手术组(Sham组)和体外循环组(CPB组),Sham组建立CPB模型管道,不进行体外循环;CPB组建立体外循环后流量逐步调至最大[≥100 ml/(kg·min)]维持转流60 min。于转流开始前(T0)和转流结束后(T1)、术后1 h(T2)、术后2 h(T3)、术后12 h(T4)行血清肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)因子检测及动脉血气分析。术后12 h(T4)获取支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织检测TNF-α、MMP-9浓度及肺组织和和核转录因子NF-κB(nuclear transcription factor-Kappa B,NF-κB)的表达水平,并行组织学检查。结果 CPB组CPB后大鼠血清、肺组织及BALF中炎症因子TNF-α、MMP-9均较Sham组明显上升,CPB组肺组织NF-κB蛋白表达水平显著高于Sham组(P<0.05);组织学检查发现CPB组表现为中性粒细胞浸润、肺间质水肿、出血、透明膜形成和坏死等病理变化。结论 CPB可导致肺组织NF-κB激活,上调TNF-α、MMP-9等炎症因子表达,引起肺损伤。

Objective To investigate the influence of cardiopulmonary bypass （CPB） on lung injury in rats and its related mechanism. Methods Twenty four male Sprague Dawley rats were randomly divided into two groups ： sham operation group （Sham） and CPB group. Sham group establish CPB model, but without CPB bypass. After establish the CPB, the flow rate was gradually adjusted to the maximum[ i〉 100 ml/（ kg min）l and maintained for 60 rain. Blood samples were collected at the beginning and the end of CPB, 1 h,2 h, 12 h for assays of tumor necrosis factor-α （TNF-α）, matrix metalloproteinase-9 （MMP-9） and arterial blood gas analy- sis. Bronchoalveolar lavage fluid （BALF） and lung tissue were obtained 12 h after the operation for detection of TNF-α, MMP-9 and NF-KB protein expression levels, histological examination was also performed. Results Compared with Sham group, inflammatory cyto- kines of TNF-α,MMP-9 of the CPB group in serum,lung tissue and BALF significantly increased and NF-KB protein expression levels in the lung samples were obviously higher after CPB （P 〈 0.05）. Histological examination revealed that the CPB group showed neutro- phil infiltration,interstitial pulmonary edema, hemorrhage, hyaline membrane formation and necrosis. Conclusion Lung injury induced by CPB is related to NF-KB activation and thus increase of TNF-α,MMP-9.