丙酮酸乙酯联合乌司他丁对大鼠重症急性胰腺炎肺损伤的保护作用

目的 观察丙酮酸乙酯联合乌司他丁对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)肺损伤的保护作用.方法 50只雄性Sprague-Dawley(SD)大鼠随机分为五组:假手术(sham-operated,S)组、SAP组、丙酮酸乙酯(ethyl pyruvate,EP)组、乌司他T(ulinastain,U)组和丙酮酸乙酯联合乌司他T(EP+U)组.除S组外,其余各组均通过逆行性胰胆管注射5%牛磺胆酸钠诱导重症急性胰腺炎模型,关腹6 h及12 h后分别处死两时间点的大鼠,酶法检测血清淀粉酶(amylase,AMY)水平,计算肺脏的湿干比重,ELISA法检测肺脏中的高迁移率蛋白-1(high mobility group Box1,HMGB-1)、肿瘤坏死因子-α(tumor necrosis factor α,TNF-α),观察胰腺和肺脏组织的形态学改变.结果 (1)SAP组大鼠肺脏表现典型的病理变化,包括肺组织间质水肿,肺泡壁增厚,肺大泡或形成局灶性肺不张.EP、U单用或联合均可减轻SAP肺的炎症反应;(2)SAP组血清AMY、肺湿干比均高于相同时间点其他各组水平(P<0.05);(3)SAP组,6 h肺组织TNF-α水平较12 h高,12 h HMGB-1水平较6 h高;(4)EP+U组肺组织HMGB-1水平均较相同时间点EP及U组低(P<0.05).结论 (1)TNF-α仅及HMGB-1均参与大鼠重症急性胰腺炎肺损伤的过程;(2)丙酮酸乙酯、乌司他丁都能减轻SAP肺损伤,联合用药作用更好.

Potective function of ethyl pyruvate combined with ulinastain on lung injury associated with severe acute pancreatitis

Objective To observe protective of ethyl pyruvate combined with ulinastain on lung injury associated with severe acute pancreatitis(SAP).Methods Fifty male Sprague-Dawley rats were randomly divided into five groups: sham-operated(S) group,SAP group,ethyl pyruvate(EP) group,ulinastain(U) group and ethyl pyruvate+ulinastain(EP+U) group.The SAP rat model was induced by retrograde injection of 5% sodium taurocholate into pancreatic bile duct except for group S.Samples of blood and tissues were collected 6 h and 12 h after the operation.The serum amylase was measured with enzymatic method,lung wet-to-dry-weight(W/D) ratios was caculated;and the concentration of HMGB-1,TNF-α in lung tissue were detected with ELISA,and pathological changes of multiple organs were observed under light microscope.Results(1)Typical SAP pathological change was found in SAP group,including pulmonary interstitial edema,pulmonary big bubble or focal atelectasis.The inflammation was relieved in SAP rats treated with ethyl pyruvate,ulinastain or the combination of both drugs;(2)Serum AMY and lung W/D ratios in SAP group were more than the other groups at the same point(P<0.05);(3)The level of TNF-α in the lung tissue was decreased significantly in SAP group at 12 h compared with 6 h,however,HMGB-1 was opposed to TNF-α;(4)The level of HMGB-1 in EP+U group was less than EP or U group at the same point(P<0.05).Conclusion(1)TNF-α and HMGB-1 are important pathogenetic factors of lung injury associated with SAP;(2)Ethyl pyruvate and ulinastain can decrease the degree of lung injury associated SAP,and the better effect may result from combination of ethyl pyruvate with ulinastain.