甘氨酸对急性坏死性胰腺炎大鼠早期外周血中性粒细胞CD11b/CD18表达的影响

目的探讨急性坏死性胰腺炎早期外周血中性粒细胞（PMN）膜上CD11b／CD18及血中IL-6、LPS的动态变化及甘氨酸对急性坏死性胰腺炎（ANP）大鼠的保护作用。方法采用5％牛磺胆酸钠逆行胆胰管注射建立大鼠ANP肝损害模型，90只大鼠，随机分成三组。30只大鼠作为对照组，甘氨酸腹腔注射治疗30只，急性坏死性胰腺炎组30只，于不同时间取血作流式细胞仪分析，测定血IL-6、LPS含量变化。结果建立ANP模型后6、12、24h，外周血中性粒细胞（PMN）膜上CD11b／CD18及血中IL-6、LPS明显升高。甘氨酸治疗后，PMN CD11b／CD18表达及IL-6、LPS水平降低。结论CD11b／CD18表达和IL-6、LPS参与急性坏死性胰腺炎的病理机制。急性坏死性胰腺炎外周血中性粒细胞（PMN）膜上CD11b／CD18的变化可能与炎性介质的变化密切相关。甘氨酸可降低CD11b／CD18表达和IL-6、LPS的水平。     

CO_2气腹对大鼠重症急性胰腺炎胰腺病理及IL-1、IL-6、CD11a/CD18和CD11b/CD18的影响

目的研究腹腔镜手术时CO2气腹对Sprague-Dawley(SD)大鼠重症急性胰腺炎(SAP)胰腺组织病理学改变、血淀粉酶、炎症细胞因子(IL-1和IL-6)和可溶性黏附分子(CD11a/CD18和CD11b/CD18)的影响。方法雄性SD大鼠50只,随机分为3组:CO2气腹组(n=20),5%牛磺胆酸钠胆胰管逆行注射方法制备SAP动物模型后,以气腹机向大鼠腹腔内注入CO2〔压力12mmHg(1mmHg=0.133kPa),维持30min〕;SAP组(n=20):建立SAP模型后关腹,不充入CO2;单纯手术组(n=10):仅开腹翻动胰腺后关腹。各组均于术后2.5h处死动物,取静脉血测定血淀粉酶、IL-1和IL-6水平及CD11a/CD18和CD11b/CD18的表达阳性率,并进行胰腺组织病理学检查。结果与单纯手术组相比,CO2气腹组和SAP组胰腺组织病理学评分、血清淀粉酶、IL-1和IL-6水平及CD11a/CD18和CD11b/CD18表达阳性率均明显升高,差异有统计学意义(P=0.000)。与SAP组相比,CO2气腹组血IL-1和IL-6水平明显降低,差异有统计学意义(P=0.000);而胰腺组织病理学评分(P=0.294)、血清淀粉酶水平(P=0.073)、CD11a/CD18(P=0.155)和CD11b/CD18(P=0.201)表达阳性率的差异无统计学意义。结论对于SAP大鼠,CO2气腹对IL-1和IL-6水平有一定的抑制作用;而对胰腺病理变化及CD11a/CD18和CD11b/CD18表达阳性率无明显影响。     

皮质醇对整合素家族细胞粘附分子CD11a/CD18、CD11b/CD18在大鼠急性坏死性胰腺炎合并多器官损伤白细胞表面表达的影响

我们应用流式细胞术检测了整合素家族细胞粘附分子CD11a/CD18和CD11b/CD18在大鼠急性坏死性胰腺炎(ANP)合并多器官损伤的模型血中白细胞表面的表达,探讨皮质醇在ANP合并多器官损伤中的作用及其机制。 一、材料与方法 1.动物模型制作方法:SD大鼠雌雄不拘,体重300～350g。随机分成ANP     

乌司他丁对急性坏死性胰腺炎发作时胰腺组织CD4、CD8的影响

目的:探讨乌司他丁对急性坏死性胰腺炎(ANP)发作时胰腺组织局部免疫功能的影响.方法:健康的SD大鼠50只随机分成4组:正常对照组(A组)20只;假手术组(B组)10只;ANP未处理组(C组)10只;ANP乌司他丁治疗组(D组)10只.ANP动物模型建立后2 h、6 h、8 h、10h分别检测AMS、NO、TNFα浓度变化及胰腺大体观察及CD4、CD8计数.结果:动物模型建立后2 h、6 h、8 h、10 h,D组AMS、NO、TNFα浓度明显低于C组(P<0.01).胰腺组织C组CD8计数明显高于D组,而CD4计数、CD4/CD8比值明显低于D组.结论:乌司他丁除了具有抑制胰酶和细胞因子的作用外,还可通过改善细胞免疫功能而达到治疗急性坏死性胰腺炎的作用.     

清胰颗粒对重症急性胰腺炎大鼠肠黏膜屏障的保护作用

目的:探讨复方中药提取物清胰颗粒对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠肠黏膜屏障的影响。方法:96只健康雄性Wistar大鼠,随机分为假手术组、SAP组和清胰颗粒组。采用胆胰管逆行注射3.5%牛磺胆酸钠建立SAP动物模型,假手术组以同样方法注射生理盐水,清胰颗粒组于造模前2h、造模后6h、18h、30h和42h分别给予清胰颗粒灌胃;SAP组仅给予安慰剂。各组大鼠分别于造模后6h、12h、24h、48h取腹主动脉血行淀粉酶和二胺氧化酶的检测,取胰腺和末端回肠组织行HE染色和病理学评分。结果:与SAP组比较,清胰颗粒组于造模后12h、24h和48h血清淀粉酶降低(P﹤0.05),于造模后24h和48h二胺氧化酶活性降低(P﹤0.05),胰腺和回肠末端病理学评分分别于造模后24h和48h降低有显著性差异(P﹤0.05)。结论:清胰颗粒能够减轻重症急性胰腺炎大鼠胰腺损伤,降低肠黏膜通透性,对重症急性胰腺炎大鼠肠黏膜屏障具有保护作用。     

蛋白酶激活受体-2在重症急性胰腺炎中的作用

目的 探讨蛋白酶激活受体-2(PAR-2)在大鼠重症急性胰腺炎病理损害中发挥的作用.方法 由大鼠胰胆管逆行注射3.5%牛磺胆酸钠,制作坏死性胰腺炎模型.36只大鼠被随机分为对照组、胰腺炎组、胰腺炎+皮下活化肽组(给药组),造模后3 h取材.免疫组化方法测定造模前后胰腺组织PAR-2表达情况变化;胰腺损害程度采用病理评分评价;测定胰腺组织湿/干重比、髓过氧化物酶含量,通过股静脉注射Evans blue(EB)测定EB漏出率;ELISIA方法测定血清IL-6水平.结果 正常胰腺组织胞浆及胞膜弱表达PAR-2,造模后表达升高.给药组病理评分、湿/干重比、髓过氧化物酶含量、Evans blue漏出率、血清IL-6水平明显低于胰腺炎组,胰腺病理评分与IL-6之间存在相关关系.结论 诱导重症急性胰腺炎后胰腺PAR-2表达升高,PAR-2可明显减轻胰腺炎症程度,对胰腺局部损害起保护作用.     

胆胰和胃冲剂对大鼠重型急性胰腺炎合并肺损伤的治疗作用

目的 :探讨胆胰和胃冲剂对大鼠重型急性胰腺炎早期肺损伤的保护作用 ,并阐明其作用机理。 方法 :SD大鼠96只 ,复制重型急性胰腺炎模型 ,并设假手术组、重型急性胰腺炎组及胆胰和胃冲剂治疗组 ,分别于模型制作后 2h、6h、12h、2 4h检测各组动物血清肿瘤坏死因子 -α (TNF -α)、内皮素 (ET)、动脉血氧分压 (PO2 )的含量及肺脏病理情况。 结果 :重型急性胰腺炎各组的TNF -α、ET含量与假手术组各相同时段相比明显升高 (P <0 0 5 ) ,PO2 (除 2h组 )含量与假手术组各时段相比明显下降 (P <0 0 5 ) ;治疗 2h组与重型急性胰腺炎 2h组各指标相比无明显差异 (P >0 0 5 ) ;治疗 6、12、2 4h组TNF -α、ET含量与重型急性胰腺炎组各相同时段相比明显下降 ,PO2 明显升高 (P <0 0 5 )。 结论 :重型急性胰腺炎时可导致肺损伤 ,胆胰和胃冲剂能调控炎症介质的释放 ,降低肺毛细血管通透性而减轻肺损伤。     

姜黄素对大鼠重症急性胰腺炎肾脏iNOS表达的影响及其保护机理研究

目的探讨姜黄素对大鼠重症急性胰腺炎肾脏诱生型一氧化氮合酶(inducible nitric oxide synthase,i NOS)m RNA表达的影响和相关性肾损伤的保护作用及其机理。方法将健康SD大鼠24只随机均分为对照组、重症胰腺炎相关性肾损伤组(简称损伤组)和姜黄素治疗组(简称治疗组),对照组和损伤组大鼠在造模前3 h分别予以1.5 m L的生理盐水灌胃,而治疗组大鼠于造模前3 h则予以1.5 m L姜黄素(200 mg/kg)生理盐水稀释液灌胃。损伤组和治疗组采用胰头夹闭法建立重症急性胰腺炎模型,造模后12 h,对照组和损伤组大鼠予以1.5 m L生理盐水灌胃,治疗组则予以1.5 m L姜黄素生理盐水稀释液灌胃。于造模后18 h采集大鼠下腔静脉血检测其血清淀粉酶、肌酐、尿素氮水平,同时采用酶联免疫吸附试验(ELISA)检测血清IL-1β、IL-6和IL-10含量;取左肾组织行病理组织学观察及采用TUNEL染色法检测肾脏细胞凋亡情况;取右肾组织采用实时-定量聚合酶链反应(RT-PCR)检测i NOS m RNA的表达。结果损伤组和治疗组大鼠血清淀粉酶、肌酐和尿素氮浓度,IL-1β、IL-6和IL-10水平,肾脏细胞凋亡指数,以及i NOS m RNA相对表达量均显著高于对照组(P0.05),而治疗组的上述指标除IL-10水平高于损伤组(P0.05)外,其余指标均低于损伤组(P0.05)。结论姜黄素对大鼠重症急性胰腺炎相关性肾损伤有较好的治疗作用;其作用机理可能与姜黄素通过抑制促炎性因子IL-1β及IL-6的表达,促进抗炎性因子IL-10的表达,下调i NOS m RNA的表达,以减少氧自由基的生成和NO对细胞的损害,从而减少肾脏的细胞凋亡及坏死有关。     

大承气汤和活血清胰汤对重型急性胰腺炎肺损伤治疗的实验研究

目的:研究重型急性胰腺炎(SAP)急性肺损伤的发生机制以及中西医结合治疗的机理.方法:应用大鼠重型急性胰腺炎模型,对比观察大承气汤(DT)、活血清胰汤(HQ)和善得定(SS)三种治疗方法对SAP模型大鼠肺泡巨噬细胞计数、活性以及巨噬细胞分泌的肿瘤细胞坏死因子(TNF)、白细胞介素-1(IL-1)和白细胞介素-6(IL-6)的影响.结果:SAP模型组肺泡巨噬细胞计数及活性、IL-1、IL-6和TNF明显高于对照组(P＜0.01),各治疗组肺泡巨噬细胞计数及活性、IL-1、IL-6和TNF明显低于SAP模型组(P＜0.05).结论:在SAP急性肺损伤中巨噬细胞聚集于肺泡并分泌大量细胞因子,大承气汤、活血清胰汤和善得定可以抑制肺泡巨噬细胞活化和分泌细胞因子,从而对SAP急性肺损伤起到保护作用.     

热休克蛋白70对急性胰腺炎时TNF、IL-8的影响

目的 探讨热休克蛋白70(Hsp70)对急性胰腺炎时TNF、IL-8的影响。方法 温生理盐水(42℃)持续灌洗大鼠腹腔30min,10 h后诱导大鼠急性胰腺炎(AP),术后2、6 h检测血清淀粉酶、TNF、IL-8水平,观察病理改变。结果 与正常AP组相比,42℃生理盐水腹腔持续灌洗预处理能明显降低AP术后2 h时的淀粉酶水平、病理评分和6 h的淀粉酶、病理评分、TNF和IL-8水平(P<0.05)。结论 42℃生理盐水腹腔持续灌洗能诱导大鼠胰腺表达Hsp70,诱导表达的Hsp70能减轻AP时的胰腺局部损伤和全身炎症反应。     

Effects of dopexamine on acute necrotising pancreatitis in rats.

OBJECTIVE: To examine the effects of dopexamine on pancreatic tissue oxygen tension (PtO2) and the extent of acinar injury in rats with acute necrotising pancreatitis DESIGN: Laboratory study. SETTING: Medical school, Turkey. ANIMALS: 68 Sprague Dawley rats. MAIN OUTCOME MEASURES: Cardiorespiratory measurements, pancreatic PtO2, effects on activity of serum amylase and concentration trypsinogen activation peptide (TAP). and histological picture. RESULTS: The four study groups (sham + saline, sham + dopexamine, acute pancreatitis and acute pancreatitis + dopexamine) were each divided into two; in 9 rats in each, pancreatic biochemistry was studied, and in the remaining 8 in each group serum biochemistry and histology were studied. The groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, packed cell volume, and serum amylase activity. The use of dopexamine increased pancreatic PtO2 in the sham + dopexamine group without the important blood pressure changes. The induction of pancreatitis resulted in a significant reduction in pancreatic PtO2 in the pancreatitis groups. The use of dopexamine did not increase pancreatic PtO2. There were no significant differences in plasma TAP concentration and the extent of acinar cell injury in the animals in the pancreatitis groups. CONCLUSION: Treatment with dopexamine does not improve the pancreatic microcirculation or reduce the extent of acinar cell injury in acute necrotising pancreatitis and is therefore unlikely to be of benefit in patients with pancreatitis.     

N-乙酰半胱氨酸对大鼠急性坏死性胰腺炎胰腺损伤的影响

目的 探讨急性坏死性胰腺炎(ANP)胰腺损伤与核因子-κB(NF-κB)活化、胰腺细胞凋亡的关系及N-乙酰半胱氨酸(NAC)对胰腺损伤的影响.方法 33只Wistar大鼠分为正常对照、盐水对照和胰腺炎组.以3.5%牛磺胆酸钠逆行注入胰胆管制作ANP模型,于造模前、后1 h应用NAC,12 h后取材,采用凝胶电泳迁移率实验测定胰腺组织NF-κB活性、改良TUNEL法检测细胞凋亡.同时观察血淀粉酶、脂肪酶、胰腺组织湿/干重比率及病理改变. 结果盐水对照组NF-κB活性很低(2.00±0.33),胰腺炎组NF-κB明显活化(6.03±0.41),造模前使用NAC抑制NF-κB活性(3.28±0.42),降低淀粉酶及胰腺湿/干重比率,促进胰腺细胞凋亡(P<0.05).NF-κB活化与凋亡呈负相关(r=-0.96,P<0.01),与胰腺损伤病理呈正相关(r=0.63,P<0.01);胰腺损伤病理分级与凋亡呈负相关(r=-0.98,P<0.01).结论 NAC可能通过抑制胰腺NF-κB活化、促进胰腺细胞凋亡,减轻胰腺损伤.     

吴茱萸次碱治疗重症急性胰腺炎的实验研究

目的：探讨吴茱萸次碱对大鼠重症急性胰腺炎（SAP）的疗效及其机制。 方法：50只SD大鼠随机均分为假手术组和4个实验组,实验组大鼠以5%牛磺胆酸钠胰胆管逆行注射制作SAP模型后,分别给予生理盐水、乌司他丁、吴茱萸次碱、乌司他丁+吴茱萸次碱处理。术后24 h,行病理学检查,并检测各组血清淀粉酶活性及血浆与胰腺组织和内皮素1（EF-1）、降钙素基因相关肽（CGRP）水平。 结果：除假手术组外,各实验组大鼠均胰腺组织均出现不同程度的胰腺炎病理改变;与假手术组比较,各实验组均出现不同程度的血清淀粉酶活性升高,血浆与胰腺组织ET-1浓度增加,而血浆与胰腺组织CGRP含量在吴茱萸次碱处理组与联合用药组均明显升高（均P<0.05）,其余实验组无明显改变（均P>0.05）;实验组中,各药物处理组胰腺病变程度、血清淀粉酶活性、血浆与胰腺组织ET-1浓度均较生理盐水处理的模型组明显降低,且均以联合用药组最为明显（均P<0.05）。 结论：吴茱萸次碱对大鼠SAP具有治疗作用,其作用可能与增加CGRP水平从而改善胰腺组织微循环有关。     

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.     

Reticuloendothelial system blockade promotes progression from mild to severe acute pancreatitis in the opossum

OBJECTIVE: To examine the relation between hepatic reticuloendothelial system (RES) dysfunction and the development of acute biliary pancreatitis. In an opossum model, the authors tested the hypothesis that RES blockade can turn the mild pancreatitis seen after pancreatic duct obstruction (PDO) into the severe form. SUMMARY BACKGROUND DATA: Biliary obstruction is considered the decisive event in gallstone pancreatitis. Suppression of the RES occurs during biliary obstruction. METHODS: Eighteen opossums were placed into three groups of six animals each: group A, RES blockade with lambda-carrageenan; group B, PDO; and group C, PDO and RES blockade with carrageenan. The severity of pancreatitis was evaluated by enzyme serum levels and percentage of pancreatic tissue necrosis. RES capacity was measured by dynamic liver scintigraphy, and hepatic blood flow was documented using the hydrogen clearance technique. RESULTS: No changes in hepatic blood flow occurred in groups A to C. RES capacity was suppressed in groups A and C; in group B, RES function remained unchanged. In group A, amylase and lipase levels remained normal, 3 +/- 1.9% of pancreatic tissue were necrotic. The animals in group B developed mild edematous pancreatitis with an increase in amylase and lipase levels and 15 +/- 10% of pancreatic necrosis. In group C, amylase and lipase increased significantly and histology revealed severe necrotizing pancreatitis, with 72 +/- 11% of necrotic areas. CONCLUSIONS: Artificial RES blockade can promote the progression from mild pancreatitis as observed after PDO to the severe necrotizing form of the disease. Thus, RES dysfunction resulting from biliary obstruction might be an important cofactor in the pathogenesis of bile-induced pancreatitis.     

Catalytic activity of phospholipase A<Subscript>2</Subscript> in blood plasma and pancreatic tissue perfusion in early experimental acute pancreatitis

BACKGROUND: To investigate the sequence of changes in the catalytic activity of phospholipase A2 in plasma and pancreatic tissue perfusion and oxygenation in mild and severe acute pancreatitis in pigs. METHODS: Twenty-four pigs were randomized into the groups of severe acute pancreatitis, mild acute pancreatitis, and controls. The pancreatic duct of eight anesthetized and mechanically ventilated pigs was cannulated, and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductal saline and developed mild acute pancreatitis. Eight pigs were cannulated only and served as controls. RESULTS: Central hemodynamics, arterial blood gases, and acid-base balance were stable throughout the study period in all three groups. Pancreatic tissue oxygenation decreased in pigs with severe acute pancreatitis and increased in animals with mild acute pancreatitis. The catalytic activity of phospholipase A2 in plasma remained stable, and there was no difference between the groups. Similarly, C-reactive protein values remained within the normal range during the study period in all groups. CONCLUSION: Plasma phospholipase A2 levels do not react to the changes in pancreatic tissue perfusion in the early phase of mild and severe acute pancreatitis.     

Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome

BACKGROUND: Select pancreatic enzymes, primarily elastase, precipitate pulmonary injury similar to pancreatitis-associated adult respiratory distress syndrome and stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF-kappaB) activation. This study explores the effect of systemic pancreatic enzymes on pulmonary NF-kappaB and inhibitory kappa B (IkappaB) proteins and their role in enzyme-induced pulmonary injury. METHODS: Mice received pancreatic elastase, amylase, lipase, or trypsin intraperitoneally. Bronchoalveolar lavage IkappaBalpha/IkappaBbeta proteins were measured by immunoblot. Pulmonary NF-kappaB activation, tumor necrosis factor (TNF) gene expression, and neutrophil infiltration (myeloperoxidase) were determined and myeloperoxidase experiments repeated in p55 TNF receptor-deficient (TNF KO) animals. Additional animals received pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB activation, and TNF protein and pulmonary microvascular permeability were measured after elastase administration. RESULTS: Pancreatic elastase induced pulmonary IkappaBalpha/IkappaBbeta degradation (30 minutes), NF-kappaB activation (60 minutes), and TNF gene expression (60 minutes) with subsequent neutrophilic inflammation (4 hours) and microvascular leakage (24 hours), whereas amylase, lipase, and trypsin did not. Furthermore, lung injury was markedly reduced in TNF KO animals and PDTC significantly attenuated TNF production and pulmonary microvascular leakage. CONCLUSIONS: Pancreatic elastase induces cytokine-mediated lung injury and this pathway involves the NF-kappaB second messenger system, further supporting elastase as a factor linking pancreatic inflammation to systemic illness during severe acute pancreatitis.     

罗格列酮对重症急性胰腺炎大鼠胰腺组织STAT1的影响

目的 探讨罗格列酮对重症急性胰腺炎(SAP)大鼠胰腺组织信号转导与转录激活因子1(STAT1)的影响.方法 将54只Wistar大鼠随机分为假手术组(S0组)、重症急性胰腺炎组(SAP组)、罗格列酮预处理组(ROSI组),每组18只.逆行胆胰管注射5%牛磺胆酸钠制备SAP模型.ROSI组造模前30 min经股静脉注射罗格列酮(6 mg/kg),然后制备SAP模型.术后3、6、12 h心脏取血处死大鼠,每个时间点6只,测定血清淀粉酶水平,胰腺组织病理切片HE染色后评分;免疫组织化学方法检测胰腺组织磷酸化STAT1蛋白的表达情况;RT-PCR测定胰腺组织肿瘤坏死因子-α(TNF-α)mRNA的表达水平.结果 SAP组各时间点磷酸化STAT1蛋白、TNF-α mRNA的表达水平、血清淀粉酶及胰腺组织光镜下病理评分较SO组显著升高(P<0.01);ROSI组各时间点上述指标较SAP组降低(P<0.05),但较SO组增高(P<0.05).结论 SAP时胰腺组织STAT1活化;罗格列酮对SAP大鼠具有保护作用,其机制可能是通过抑制Janus激酶-信号转导与转录激活因子通路来抑制其下游炎性介质的产生.     

Diminished lung injury with vascular adhesion molecule-1 blockade in choline-deficient ethionine diet-induced pancreatitis

BACKGROUND: Lung injury in severe acute pancreatitis is mediated by infiltrating leukocytes. Our laboratory has previously demonstrated that acute lung injury in acute pancreatitis results in an up-regulation of vascular adhesion molecule-1 (VCAM-1) cell surface receptor expression on pulmonary vascular endothelium and neutrophil sequestration. The objective of this study was to determine whether blocking expression of VCAM-1 in acute pancreatitis would modify acute pulmonary injury. METHODS: Young female mice were fed a choline-deficient ethionine (CDE) supplemented diet to induce acute pancreatitis. After initiation of the diet, one group (acute pancreatitis treated [n = 18]) was treated with blocking doses (2.35 mg/kg) of monoclonal anti-VCAM-1 receptor antibody (Ab) at 48, 96, and 120 hours. A second group (acute pancreatitis treated control [n = 5]) was treated with a similar dose of an isotypic control for VCAM-1 (nonbinding Ab) at the same time points. A third group (acute pancreatitis untreated [n = 12]) received a CDE diet, and a fourth group (control [n = 11]) received standard food with no Ab treatment. All animals were killed at 144 hours. The dual radiolabeled monoclonal Ab method was used to quantitate VCAM-1 cell surface expression in lung tissue. Lung injury was assessed histologically, and apoptosis was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. Pulmonary leukocyte sequestration was determined by myeloperoxidase (MPO) assay and CD18 staining. RESULTS: Pulmonary VCAM-1 cell surface expression was significantly increased in animals with acute pancreatitis when compared to controls (P <.001) and was reduced to near control levels in acute pancreatitis treated animals. On histologic examination, treated animals with acute pancreatitis exhibited significantly less lung injury and apoptosis than did untreated animals with acute pancreatitis. Leukocyte sequestration and MPO activity were significantly reduced in the treated animals with pancreatitis compared to untreated animals with pancreatitis (P <.0001) or acute pancreatitis treated controls (P <.03). CONCLUSIONS: Blocking VCAM-1 on pulmonary vascular endothelium decreases leukocyte adherence and recruitment into the lung, hence reducing lung injury in severe acute pancreatitis. Clinically, VCAM-1 antagonism may be an important adjunct to evolving therapy for distant organ injury in severe acute pancreatitis.