一氧化碳释放分子对重症急性胰腺炎肺损伤保护作用的实验研究

目的 探讨一氧化碳释放分子(CORM-2)对大鼠重症急性胰腺炎(SAP)肺损伤的保护作用及机制.方法 30只雄性Wistar大鼠随机分为3组(n=10):sham组、SAP组,CORM-2组.以3.5%牛磺胆酸钠逆行注射胰胆管的方法制作SAP模型.CORM-2组于SAP造模0.5 h后经阴茎背动脉注射CORM-2(8 mg/kg).各组均于造模6 h后取材,测定血清肿瘤坏死因子-α(TNF-α)含量;采用RT-PCR法检测肺组织细胞因子诱导的中性粒细胞趋化因子(CINC)及细胞间黏附分子-1(ICAM-1)mRNA的表达;同时检测肺组织髓过氧化物酶(MPO)活性、湿/干重比及对肺脏进行病理学评分.结果 与SAP组相比,CORM-2组血清TNF-α水平、肺组织病理损伤程度、湿/干重比、MPO活性、CINC及ICAM-1 mRNA的表达均显著降低(P＜0.05).结论 应用CORM-2能够降低血清TNF-α水平、下调肺组织CINC及ICAM-1 mRNA的表达,进而有效地抑制肺组织中性粒细胞的大量浸润,从而对SAP肺损伤起到明显的保护作用.

An experimental study on protective effect of carbon monoxide releasing molecule on severe acute pancreatitis induced lung injury

Objective To investigate the protective effect of carbon monoxide releasing molecule (CORM-2) on severe acute pancreatitis (SAP) induced lung injury in rats.Methods Thirty male Wistar rats were randomly divided into three groups (n= 10) including sham group, SAP group and CORM-2 group.The model of SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatobiliary duct.CORM-2 (8 mg/kg) was infused through the dorsal artery of penis 0.5 h after establishing the model of SAP in CORM-2 group.All animals were sacrificed 6 h after SAP in-duction.The serum level of tumor necrosis factor-α (TNF-α), pulmonary cytokine induced neutrophil chemoattractant (CINC), intercellular adhesion molecule-1 (ICAM-1) mRNA expression as well as the activity of myeloperoxidase (MPO) in the lung were examined in each group.The wet/dry ratio of the lung was also determined.The lung was scored on the basis of pathological changes.Results Compared with SAP group, pulmonary over-expression of CINC and ICAM-1 mRNA was obviously inhibited in CORM-2 group and the serum TNF-α level, the MPO activity in lung tissue, the wet/dry ratio of lung, and the pathological score of lung injury were significantly lower (P＜0.05).Conclusion Administration of CORM-2 can remarkably reduce the severity of SAP induced lung injury through in-hibiting the over-expression of CINC and ICAM-1 mRNA, down-regulating the serum TNF-α level and subsequently decreasing pulmonary neutrophil infiltration.