重症急性胰腺炎器官损伤与内皮素-1mRNA表达的关系及丹参的影响

目的探讨重症急性胰腺炎(SAP)内皮素-1(ET-1)mRNA表达对胰腺及肺、肾损伤的作用机制,观察丹参注射液对ET-1mRNA表达及病情转归的影响。方法将Wistar大鼠随机分为模型组(n=15)、丹参组(n=15)、对照组(n=15)。建立SAP模型后,丹参组动物立即肌肉注射丹参注射液(每日2ml/kg体重),每6h1次,共给药4次。对照组仅行假手术。各组动物在术后24h测血淀粉酶、ET-1和腹水量。使用原位杂交和图像分析检测胰、肺、肾ET-1mRNA的表达强度,并观察胰、肺、肾病理变化。结果模型组血中淀粉酶(2156.05±355.87)U/L和腹水量(9.87±2.34)ml显著高于丹参组(1439.21±332.99)U/L、(5.27±2.81)ml和对照组(215.67±37.27)U/L、0ml(P<0.01)。模型组血中ET-1(185.47±20.80)ng/L高于丹参组(164.27±18.53)ng/L和对照组(72.90±17.27)ng/L(P<0.05,P<0.01)。模型组胰、肺、肾中ET-1mRNA表达显著高于丹参组(P<0.01)。丹参组胰、肺、肾病理改变较模型组减轻。结论SAP时胰腺的ET-1mRNA高表达导致ET-1过度生成并可能继发引起肺、肾病理损害。丹参能抑制胰腺的ET-1mRNA的过度表达,减轻血管内液体丢失,改善血流动力学,从而对胰腺及肺、肾组织起保护作用。     

氯化镧对内毒素/脂多糖诱导巨噬细胞株一氧化氮合酶表达的抑制作用

目的了解氯化镧（LaCl3）对内毒素／脂多糖（LPS）刺激的巨噬细胞诱导型一氧化氮合酶（iNOS）表达的影响，并探讨其机制。方法将小鼠巨噬细胞株RAW264．7分为空白对照组、LaCl、组、LPS组和LaCl3＋LPS组。前3组细胞分别用常规培养液、含2．50μmol／L LaCl3的培养液、含1mg／L LPS的培养液培养24h，LaCl3＋LPS组用含2．5μmol／LLaCl，的培养液培养24h后，换为含1mg／L LPS的培养液培养24h。采用免疫细胞化学染色法检测iNOS在各组细胞中的表达强度；蛋白质印迹法检测iNOS的蛋白表达水平；反转录一PCR测定iNOS的mRNA表达水平；硝酸还原酶法测定各组细胞培养上清液中一氧化氮（NO）含量。结果免疫细胞化学染色结果显示，iNOS主要分布于各组细胞的胞质中，空白对照组和LaCl3组荧光强度极弱；LPS组荧光强度最强，阳性细胞百分率为44．4％，明显高于LaCl3＋LPS组（11．8％，P〈0．05）。LPS组iNOS蛋白及其mRNA表达量和细胞培养上清液中NO含量均高于其余各组（P〈0．05）。结论LaCl3可在mRNA水平和蛋白水平抑制LPS诱导的iNOS过度表达，减少NO生成，提示LaCl3能拮抗LPS诱导的iNOS过度活化。     

白藜芦醇对重症急性胰腺炎肺损伤大鼠肺泡巨噬细胞功能的影响

目的:观察白藜芦醇(Res)对重症急性胰腺炎(SAP)大鼠肺泡巨噬细胞功能的影响。方法:36只大鼠随机分为假手术组、重症急性胰腺炎模型组(SAP)和白藜芦醇治疗组3组。制模后6h行肺、胰腺组织病程学检查。经支气管肺泡灌洗获取肺泡巨噬细胞,检测支气管肺泡灌洗液中蛋白含量、肺泡巨噬细胞肿瘤坏死因子α(TNF-α)及一氧化氮(NO)水平。以反转录聚合酶链反应(RT-PCR)法测定肺泡巨噬细胞TNF-αmRNA、诱导型一氧化氮合酶(iNOS)mRNA表达情况。结果:Res处理组6h肺支气管肺泡灌洗液中蛋白含量为(844.7±198.2)μg/mL,显著低于SAP组(P<0.05);Res处理组肺泡巨噬细胞分泌TNF-α和NO水平分别为(544.7±98.4)pg/mL和(31.7±9.8)μmol/L,显著低于SAP组(P<0.05)。Res组肺泡巨噬细胞TNF-αmRNA、iNOSmRNA的表达相对强度,亦显著低于SAP组。SAP大鼠各组指标与假手术组相比差异均有显著性意义(P<0.05)。结论:Res能显著减轻SAP时肺和胰腺组织损伤,其机制与抑制巨噬细胞功能,抑制TNF-α和iNOSmRNA表达有关。     

七氟醚对内毒素诱导大鼠肺组织氧化应激反应的影响

目的 探讨七氟醚对内毒素（LPS）诱导大鼠肺组织氧化应激反应的影响。方法Wistar大鼠48只，体重200-290g，随机分为4组（n=12）：对照组（C组）、LPS组（L组）、1．0MAC七氟醚组（S1L组）和1．5MAC七氟醚组（S2L组）。各组大鼠腹腔注射异戊巴比妥钠100mg／kg，麻醉后机械通气。维持呼气末二氧化碳分压在35～45mmHg。L组股静脉注射LPS5mg／kg，C组给予生理盐水1．2ml，S1L组、S2L组注射LPS后分别吸入1．0MAC、1．5MAC七氟醚4h。吸入七氟醚后4h处死大鼠，测定肺组织超氧化物超歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）、总一氧化氮合酶（tNOS）水平、诱导型一氧化氮合酶（iNOS）活性及iNOS mRNA、蛋白表达。结果 与C组比较，L组肺组织SOD活性下降，MDA、NO、tNOS水平、iNOS活性及iNOS mRNA及蛋白表达均升高（P〈0．01）；与L组比较，S1L组、S2L组肺组织SOD活性升高，MDA、NO、tNOS水平及iNOS mRNA及蛋白表达降低（P〈0．05）；S1L组与S2L组上述各项指标比较差异无统计学意义（P〉0．05）。结论 吸入1．0MAC和1．5MAC七氟醚4h可减轻LPS诱导肺组织氧化应激反应。     

地氟醚对内毒素诱导大鼠肺组织氧化应激反应的影响

目的探讨地氟醚对内毒素（LPS）诱导大鼠肺组织氧化应激反应的影响。方法雄性Wistar大鼠48只,体重200～290 g,随机分为4组（n=12）,对照组（C组）股静脉注射生理盐水1.2ml后机械通气4 h;LPS组（L组）股静脉注射LPS 5mg/kg后机械通气4 h;地氟醚1.0MAC组（D1）和地氟醚1.5 MAC组（D2）组：股静脉注射LPS 5 mg/kg后机械通气,分别吸入地氟醚1.0 MAC和1.5 MAC 4 h,机械通气4 h后处死大鼠,测定肺组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量、一氧化氮（NO）含量、总一氧化氮合酶（tNOS）活性、诱导型一氧化氮合酶（iNOS）活性、iNOS mRNA和iNOS表达水平。结果与C组比较,L组SOD活性下降,MDA含量、NO含量、tNOS活性、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.01）;与L组比较,D1组上述各项指标差异无统计学意义（P〉0.05）,D2组SOD活性下降,MDA含量、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.05）;与D1组比较,D2组SOD活性下降,MDA含量、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.05）。结论吸入地氟醚1.5 MAC 4 h可加重LPS诱导大鼠肺组织氧化应激反应,吸入地氟醚1.0 MAC对其无影响。     

内毒素血症时肺动脉和胸主动脉内一氧化氮合酶表达的比较

目的 观察内毒素血症时肺动脉和胸主动脉中诱导型一氧化氮合(iNOS)基因和蛋白表达的时间依从性变化。方法 48只Wistar大鼠350－450g，雌雄兼备，随机均分成对照组（C组），3h组，8h组和48h组。对照组腹腔内注射2ml生理盐水，余各实验组腹腔内注射脂多糖（LPS）4mg/kg，溶于2ml生理盐水，分别在LPS腹腔内注射后3h,8h和48h颈椎脱臼法处死大鼠取肺动脉和胸主动脉，RT－PR和Western blot法测定各组肺动脉和胸主动脉中iNOS的mRNA和蛋白表达。结果 LPS注射后大鼠肺动脉中iNOS的mRNA和蛋白表达逐渐上升，8h达到高峰，48h恢复到LPS注射前水平；胸主动脉中iNOS的蛋白表达3h即达峰值，以后逐渐下降，48h恢复到LPS注射前水平。LPS注射后3h和8h大鼠iNOS的mRNA及蛋白表达水平肺动脉比胸主动脉高。结论 内毒素大鼠的肺动脉和胸主动脉中iNOS的mRNA和蛋白的表达呈现时间依从性变化，iNOS的mRNA和蛋白表达峰值胸主动脉早于肺动脉，肺动脉中iNOS的mRNA和蛋白表达程度高于胸主动脉。     

高糖对系膜细胞诱生型一氧化氮合酶表达及细胞外基质合成的影响

目的:探讨高糖对体外培养的系膜细胞诱生型一氧化氮合酶(iNOS)mRNA表达的调节作用及NO合成的变化,以及上述变化对细胞外基质(ECM)合成的影响.方法:利用脂多糖(LPS)诱导系膜细胞表达iNOS,观察5.6、10、25、40 mmol/L不同糖浓度,在0、4、24、48 h不同时间点培养的系膜细胞iNOS mRNA表达的变化及培养上清中NO、Ⅳ型胶原、纤维连接蛋白含量的变化,以相同渗透压的甘露醇为对照组.细胞增殖测定采用MTT法,iNOS表达采用RT-PCR的方法,NO的检测采用硝酸还原法,Ⅳ型胶原、纤维连接蛋白的测定采用ELISA法.结果:高糖抑制系膜细胞增殖;LPS刺激后系膜细胞可表达iNOS;高糖浓度时iNOS mRNA表达增加,呈浓度和时间依赖性,相同渗透压的甘露醇无类似作用(P<0.01);随着糖浓度的升高和时间延长,实验组上清中NO含量增加,Ⅳ型胶原、纤维连接蛋白含量增加.结论:高糖可上调系膜细胞iNOS mRNA的表达和促进NO、Ⅳ型胶原、纤维连接蛋白的合成.     

清胰颗粒对重症急性胰腺炎大鼠回肠claudin-1表达的影响

目的观察复方中药提取物清胰颗粒对重症急性胰腺炎(SAP)大鼠回肠黏膜的保护作用及对claudin-1表达的影响。方法 96只健康雄性Wistar大鼠随机分为假手术组,SAP组,SAP+清胰颗粒(治疗)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。治疗组于制模前2 h给予清胰颗粒水溶液灌胃,以后每12 h灌胃1次。各组大鼠分别于制模后6,12,24,48 h取回肠末端HE染色观察病理改变;应用免疫组织化学法和实时荧光定量PCR法检测回肠黏膜紧密连接蛋白claudin-1的表达。结果与SAP组比较,治疗组回肠病理损伤在制模后24 h和48 h有明显改善,回肠claudin-1蛋白和mRNA表达水平在制模后12,24,48 h升高,差异均有统计学意义(P0.05)。结论清胰颗粒能通过上调肠紧密连接蛋白claudin-1的蛋白和mRNA表达,保护肠道黏膜,维护肠黏膜屏障功能。     

MCP-1在SAP大鼠胰腺及肠黏膜组织中的表达

目的 观察单核细胞趋化蛋白-1 （MCP-1）在重症急性胰腺炎（severe acute pancreastitis,SAP）大鼠血清、胰腺及肠黏膜组织中的表达并探讨其机理。方法 24只SD大鼠随机均分为对照组和SAP组。对照组大鼠开腹后仅翻动肠管,SAP组以3%牛磺胆酸钠按0.05 mL/100 g逆行注入大鼠胆胰管（注射时间1 min） 复制SAP模型。2组大鼠分别于制模后12及24 h采集血标本和胰腺及回肠组织标本,进行如下指标检测：①ELISA法测定血清中MCP-1及IL-10水平;②比色法测定淀粉酶（amylase,AMY）水平及二胺氧化酶（diamine oxydase,DAO）水平;③RT-PCR法检测胰腺及回肠组织中MCP-1 mRNA的表达;④观察胰腺及回肠组织的病理学改变。结果 SAP组血清中MCP-1、IL-10、AMY和DAO水平均较对照组升高（P＜0.01）;SAP组胰腺及回肠组织中MCP-1 mRNA表达较对照组上调（P＜0.01）,胰腺组织的病理学评分明显增高（P＜0.01）。结论 MCP-1在SAP大鼠血清、胰腺及回肠组织中的表达均上调,且加重了胰腺和肠道组织的损伤。     

硝普钠对内毒素致大鼠急性肺损伤保护作用的机制

目的 研究外源性一氧化氮（NO）供体一硝普钠对内毒索（LPS）致大鼠急性肺损伤（Au）保护作用的机制。方法 32只Wistar大鼠随机分为4组（n=8），假手术组（S组）、内毒素组（LPS组）、HO-1诱导剂氯化高铁血红素预处理组（HM组）和硝普钠治疗组（SNP组）。采用气管内滴入750μg／kg（溶于300ml生理盐水中）LPS建立大鼠ALI模型，HM组在给LPS前12h腹腔注射氯化高铁血红素40μmol／kg，SNP组将LPS与硝普钠（25μg／kg）同时滴入气管。滴人LPS后8h处死大鼠，测定肺组织湿／干重比（W／D）、丙二醛（MDA）含量、诱导型血红素加氧酶（HO-1）、诱导型一氧化氮合酶（iNOS）蛋白表达及支气管肺泡灌洗液（BALF）蛋白浓度，并观察肺组织病理变化。结果 与S组比较，LPS组、HM组、SNP组肺组织iNOS、HO-1蛋白表达均增强，LPS组、HM组肺组织W／D及MDA含量增加，LPS组BALF蛋白浓度增加；与LPS组比较，HM组和SNP组肺组织iNOS蛋白表达减弱，肺组织HO-1蛋白表达增强，肺组织W／D、MDA含量及BALF蛋白浓度降低（P〈0．05或0．01）。SNP及HM组肺组织病理损伤程度明显轻于LPS组。结论 硝普钠可通过诱导HO-1进而抑制iNOS／NO，减轻LPS所致ALI．     

Increased gut permeability following burn trauma

Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full-thickness burn injury. Gastrointestinal permeability was assessed before burn and on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary excretion for the next 7 hours. In normal guinea pigs, lactulose (molecular weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose (molecular weight, 164 d) is mostly absorbed by the transcellular route. Gut permeability to L-rhamnose did not increase after burn injury (211 micrograms before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). By contrast, gut permeability to lactulose increased significantly and was greatest in the first 48 hours after burn injury (60 micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). Gut permeability to low-molecular-weight compounds increases immediately after burn trauma, and this may be by a paracellular rather than transcellular mechanism.     

Dexamethasone reduces gut permeability in pediatric cardiac surgery

OBJECTIVES: Little attention has been paid to the effect of the systemic inflammatory response syndrome on intestinal dysfunction in the postoperative period. Several proinflammatory cytokines have been reported to increase the permeability of intestinal mucosa in vitro. We investigated the effect of dexamethasone on gut permeability in pediatric patients undergoing cardiac surgery by using the dual sugar permeability test and absorption of 2 other saccharides. METHODS: Thirty-four patients scheduled for cardiac surgery with cardiopulmonary bypass were prospectively randomized to either act as control subjects or to receive dexamethasone (1 mg . kg -1) during induction of anesthesia. Intestinal permeability was measured with 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose administered orally after induction of anesthesia and 12 and 24 hours later. RESULTS: Lactulose/rhamnose ratios were increased from the outset in both groups (mean 0.57 [95% confidence interval, 0.24-0.91] for the control group and 0.76 [95% confidence interval, 0.35-1.17] for patients receiving dexamethasone). Although the ratios decreased 12 hours (0.29 [95% confidence interval, 0.17-0.42]) and 24 hours later (0.17 [95% confidence interval, 0.08-0.15]) in the dexamethasone group, in the control group there was a rise at 12 hours (0.77 [95% confidence interval, 0-1.64]), with a slight reduction 24 hours later (0.46 [95% confidence interval, 0.06-0.85]). CONCLUSIONS: Infants and children undergoing cardiac surgery with cardiopulmonary bypass show a significant reduction in gut permeability when dexamethasone is used during induction of anesthesia. Dexamethasone does not affect the intestinal barrier at the functional level, as assessed on the basis of 3-O-methyl-D-glucose and D-xylose absorption.     

Lower limb ischaemia and reperfusion alters gut permeability.

The gut may be important in the aetiology of multiple organ failure (MOF) by amplifying of the inflammatory response to trauma. We investigated the effects of the reperfusion of ischaemic lower limbs on gut permeability. Male Wistar rats (n = 30) were randomised to (group 1) controls; (group 2) 3 h bilateral hind-limb ischaemia alone; or 3 h ischaemia followed by (group 3) 15 min reperfusion or (group 4) 2 h reperfusion. Gut permeability and plasma endotoxin were measured prior to tourniquet application, immediately before tourniquet release, and following reperfusion. To evaluate the effect of the hypotension that follows tourniquet release, (group 5) sodium nitroprusside was infused in further controls to maintain mean arterial pressure (MAP) at 75 mmHg for 2 h. Horseradish peroxidase was instilled into the isolated ileo-caecal loop 15 min before the animals were killed to measure permeability of horseradish peroxidase through mucosal intercellular tight junctions by electron microscopy. Mean arterial pressure increased from 105 +/- 5 mmHg to 136 +/- 4 mmHg on tourniquet application and fell to 79 +/- 7 mmHg following reperfusion (p less than 0.05). In group 1 (controls), group 2 (ischaemia alone animals) and group 5 (ischaemia and nitroprusside) one animal out of six demonstrated permeability to horseradish peroxidase. Following reperfusion, horseradish peroxidase permeability had not developed by 15 min (group 3) but was present in all animals by 2h (group 4) (p = 0.015 Fisher's exact test). Plasma endotoxin increased from 21.8 +/- 2.0 pg ml-1 to 30.7 +/- 2.6 pg ml-1 following 2 h reperfusion (p less than 0.05 Scheffe F-test).(ABSTRACT TRUNCATED AT 250 WORDS)     

生态免疫肠内营养对急性胰腺炎肠道通透性及感染并发症的影响

目的观察生态免疫肠内营养对急性胰腺炎肠通透性及感染并发症的影响。方法76例急性胰腺炎患者在入院48h内随机分为2组,即肠外营养组(PN组)38例和生态免疫肠内营养组(EIN组)36例,EIN组经鼻空肠营养管注入100ml植物乳酸菌(活菌,1×10~8 cfu/ml)持续7d。观察入院时和第8天APACHEⅡ、Balthazar CT评分,统计SIRS,MODS发生率,测定鼻胃管抽吸物细菌含量;入院时、支持后第5天和第8天口服乳果糖和甘露醇(L/M),采用HPLC测定尿中L/M比值;第8天测定血内毒素水平和进行肠道细菌DNA基因指纹分析;营养支持第5天测定营养治疗2h内的促胆囊收缩素和胃泌素含量;第8天统计感染性并发症的发生率和死亡率。结果EIN组获得了良好的治疗效果,感染性并发症明显降低,肠道细菌多样性和通透性得到改善,APACHEⅡ计分和死亡率明显下降,EIN组出现暂时性的CCK分泌增高,但未增加疾病负担。结论EIN能减轻疾病严重程度,改善肠道通透性,降低感染性并发症发生率。     

Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl-min^−l.cap ⁻¹ [control]; P = NS), whereas mucosal (1.59 _± 0.03 vs. 2.28 ± 0.03 nl.min^−l.cap ⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl-min^−l.cap ^-1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 = 0.03 vs. 1.98 ± 0.04 nl’min^-1.cap ^-1 [control]; P <0.01) and colonic (mucosal: 0.59 = 0.01 vs. 2.28 ± 0.03 nl.min^−l.cap ^-1 [control], P < 0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl.min^−l.cap ^-1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ±19 nmol.hr^−l.cm {−2}2; mild pancreatitis: 158±23 nmol-hr^−l.cm^-2; severe pancreatitis: 181 ±33 nmol.hr^−l.cm^-2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 19–22, 1996. Supported in part by Deutsche Forschungsgemeinschaft (DFG Fo 197/3).     

Ibuprofen improves survival but does not ameliorate increased gut mucosal permeability in endotoxic pigs.

Intravenous lipopolysaccharide (LPS) decreases superior mesenteric arterial blood flow and increases ileal mucosal permeability in pigs. We tested the hypothesis that these phenomena can be ameliorated by pretreatment and posttreatment with ibuprofen. Pentobarbital-anesthetized immature swine were mechanically ventilated (fraction of inspired oxygen, 0.5) and infused with Ringer's lactate (RL) solution (0.8 mL/kg per minute). Animals in group RL (n = 10) received no other interventions. Animals in group RL + LPS (n = 15) were infused with LPS (50 micrograms/kg) from a time range equal to 0 through 60 minutes. Animals in group RL + LPS + ibuprofen (n = 10) were similarly infused with LPS, but in addition, they received ibuprofen (10 mg/kg at -30 minutes and 10 mg/kg per hour from -30 through 210 minutes). Intestinal permeability was assessed by measuring plasma-to-lumen clearances of two hydrophilic probes (chromium 51-labeled edetic acid monohydrate [EDTA] and urea) and by expressing the results as a clearance ratio (CEDTA/CUREA). Survival was 100%, 67%, and 100% in groups RL, RL + LPS, and RL + LPS + ibuprofen, respectively. Among survivors only, CEDTA/CUREA increased significantly over time in both endotoxic groups, but not in nonendotoxic controls. Treatment with ibuprofen transiently blocked LPS-induced mesenteric hypoperfusion. These data indicate that mediators other than cyclooxygenase-derived metabolites of arachidonic acid are responsible for the adverse effect of LPS on mesenteric permeability to hydrophilic solutes in this porcine model.     

Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives

Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals.     

Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock

BACKGROUND: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. METHODS: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hgx90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. RESULTS: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. CONCLUSIONS: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.     

Multi-antioxidant supplementation does not prevent an increase in gut permeability after lower torso ischemia and reperfusion in humans

BACKGROUND: An increase in gut permeability can have serious consequences leading to sepsis and multiple organ failure. After lower torso ischemia an increase in gut permeability is seen in both animals and humans. There is proof that this can be modified by antioxidant supplementation. METHODS: In this prospective, randomized study we have looked at the influence of a multiantioxidant supplementation regime, using allopurinol, vitamins E and C, mannitol and N-acetylcysteine, perioperatively. Twenty-two patients received standard treatment and 20 patients received supplementation. Gut permeability was determined using a double sugar test with lactulose and rhamnose. RESULTS: A significant increase in gut permeability was found neither in the non-treatment group (p = 0.012) nor in the treatment group (p = 0.006) after 6 and 24 h. No difference was found between the group receiving antioxidants and the standard treatment group. p = 0.93 6 h post clamp; p = 0.97 24 h post clamp. CONCLUSION: In this study we have not found an influence of multiantioxidant supplementation on gut permeability after lower torso ischemia. Possible explanations for this negative result are being discussed.     

气相色谱用于肠通透性监测的研究

作者采用国产气相色谱及９２０２微机数据处理系统，对临床患者和实验动物肠通透性改变进行监测。该方法以甘露醇（Ｍ）和乳果糖（Ｌ）为探针，用气相色谱检测尿中糖分泌率及Ｌ／Ｍ比值。结果显示，测定标准品Ｍ和Ｌ随进样量增加而呈线性改变，与国外学者报道一致。比较不同浓度进口与国产乳果糖，证明二者在研究肠通透性方面高度相关（ｒ＝０．９９）。检测急性胰腺炎并发感染动物的尿标本，发现乳果糖大量排出，Ｌ／Ｍ值明显增加。作者认为，气相色谱为一行之有效的方法用于肠通透性监测，有助于临床上对内源性感染及脓毒症的早期诊断。