目的 探讨胆汁外引流对重症急性胰腺炎大鼠肺部炎症和水肿的疗效与机制。方法 24只雄性Sprague-Dawley（SD）大鼠随机分为4组（n=6）：假手术组（SS组）、重症急性胰腺炎组（SAP组）、SAP+胆汁外引流组（SAP+BTED组）、SAP+BTED+锌原卟啉组（SAP+BTED+ZnPP组）。ZnPP是血红蛋白氧合酶1（HO-1）的特异性阻断剂,抑制HO-1的表达。造模24 h后取肺组织和血液备用。采用Schmidt评分标准对肺组织进行病理评分。采用Western印迹法检测肺组织中HO-1蛋白质水平表达。采用荧光定量RT-PCR法检测肺组织中HO-1、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）mRNA 基因水平的表达。采用ELISA法检测肺组织中髓过氧化物酶（MPO）的含量。计算肺组织干湿比。结果 SAP+BTED组大鼠肺组织Schmidt评分显著低于SAP组大鼠（P<0.05）。BTED使肺组织中TNF-α和IL-6 mRNA 基因表达水平、MPO含量显著低于SAP组大鼠（P<0.05）。SAP+BTED组大鼠干湿比和HO-1表达水平显著高于SAP组大鼠（P<0.05）。当应用ZnPP时,BTED引起大鼠的这些效应则消失。结论 BTED通过HO-1通路减轻SAP大鼠肺部的炎症和水肿。
Objective To investigate the roles of biliary tract external drainage(BTED) on lung inflammation and edema of the rats with severe acute pancreatitis(SAP). Methods Twenty-four SD rats were randomly divided into four groups of six each: group sham surgery(SS), group SAP, group SAP+BTED with the SAP rats established first and then BTED performed, group SAP+BTED+zinc protoporphyrin (ZnPP) with Znpp injected abdominally 24 h before and then SAP with BTED procedure. ZnPP is a specific inhibitor of heme oxygenase-1(HO-1), which can inhibit the expression of HO-1. The rats were sacrificed 24 h after surgery. The lung and blood were collected. The pathological changes of lung were scored by Schmidt criterion. mRNA expression of HO-1, TNT-α and IL-6 were detected by quantitative RT-PCR method, lung HO-1 expression by Western blot and myeloperoxidase(MPO) protein by ELISA. The ratio of dry/wet of lung tissue was calculated. Results The Schmidt score in group SAP+BTED were significantly lower than in group SAP(P<0.05). The expression of both TNT-α and IL-6 with MPO level in group SAP+BTED were significantly lower than in group SAP(P<0.05). But the dry/wet ratio and the expression of HO-1 protein in group SAP+BTED were significantly increased than in group SAP(P<0.05). All these effects induced by BTED were not present when ZnPP war given. Conclusions BTED could reduce the lung inflammation and edema of the rats with SAP via the HO-1 pathway.
[1] Xue DB, Zhang WH, Yun XG, et al.Regulation effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats[J]. Chin Med J (Engl),2007,120(8):690-695.
[2] Shields CJ, Winter DC, Redmond HP.Lung injury in acute pancreatitis: mechanisms, prevention, and therapy[J]. Curr Opin Crit Care,2002,8(2):158-163.
[3] Lankisch PG, Lerch MM.The role of antibiotic prophylaxis in the treatment of acute pancrestitis[J]. J Clin Gastroenterol,2006,40(2):149-155.
[4] Mayerle J, Hlouschek V, Lerch MM.Current management of acute pancreatitis[J]. Nat Clin Pract Gastroenterol Hepatol,2005,2(10):473-483.
[5] Bhatia M, Brady M, Shokuhi S, et al.Inflammatory media-tors in acute pancreatitis[J]. J Pathol,2000,190(2):117-125.
[6] Vallabhaneni R, Kaczorowski DJ, Yaakovian MD, et al.Heme oxygenase 1 protects against hepatic hypoxia and injury from hemorrhage via regulation of celluar respiration[J]. Shock,2010,33(3):274-281.
[7] Tamion F, Richard V, Renet S, et al.Protective effects of heme-oxygenase expression against endotoxic shock: inhibition of tumor necrosis factor-alpha and augmentation of interleukin-10[J]. J Trauma,2006,61(5):1078-1084.
[8] Gao S, Wang Y, Zhao J, et al.Effects of dexmedetomidine pretreatment on heme oxygenase-1 expression and oxidative stress during one-lung ventilation[J]. Int J Clin Exp Pathol,2015,8(3):3144-3149.
[9] 宋小芹, 赵冰, 陈尔真, 等. “胆汁外引流”降低重症急性胰腺炎大鼠胰腺损伤的作用及机制研究[J]. 国际外科学杂志,2014,41(6):297-301.
[10] Guo SB, Duan ZJ, Li Q, et al.Effect of heme oxygenase-1 on renal function in rats with liver cirrhosis[J]. World J Gastroenterol,2011,17(3):322-328.
[11] Ibrahim I, El-Sayed S, Abdel-Hakim S, et al.Inhibition of endogenous CO by ZnPP protects against stress-induced gastric lesion in adult male albino rats[J]. J Physiol Biochem,2012,68(3):319-328.
[12] Schmidt J, Rattner DW, Lewandrcowski K, et al.A better model of acute pancreatitis for evaluating therapy[J]. Ann Surg,1992,215(1):44-56.
[13] 刘勇军, 毛恩强, 李磊, 等. 失血性休克大鼠器官组织中促炎细胞因子表达及释放的时相性研究[J]. 中国危重病急救医学,2007,19(5):290-294.
[14] Pastor CM, Matthay MA, Frossard JL.Pancreatitis-associa-ted acute lung injury: new insights[J]. Chest,2003,124(6):2341-2351.
[15] Tang Y, Tian H, Shi Y, et al.Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO[J]. Phytomedicine,2013,20(8-9):699-704.
[16] 王志威, 彭奕冰, 费健, 等. 血红素加氧酶-1对重症急性胰腺炎小鼠模型保护作用的实验研究[J]. 外科理论与实践,2010,15(1):19-22.
[17] 张飞虎, 费健, 黄洁, 等. 血红素加氧酶-1对重症急性胰腺炎大鼠模型胰腺和肝脏保护作用的实验研究[J]. 国际外科学杂志,2011,38(9):602-605.
