甲状腺激素对大鼠急性肝衰竭肠粘膜屏障功能影响的实验研究
|
摘要
【目的】观察大鼠急性肝衰竭时肠粘膜屏障功能损害及甲状腺激素代谢异常,探讨补充外源性甲状腺激素对损害肠粘膜屏障的影响。
【方法】SD大鼠34只,随机分为三组:①正常对照组(SO组)10只②急性肝衰竭组(AHF组)12只。③急性肝衰加甲状腺激素治疗组(AHF+TH组)12只。后两组大鼠按400mg/kg的标准腹腔内注射硫代乙酰胺(TAA),24h后用相同剂量TAA重复注射1次,模拟建立大鼠急性肝衰竭模型。AHF+TH组大鼠于造模前30min、首次腹腔注射TAA后18h、36h,分别按15μg·kg~(-1)的标准腹腔注射甲状腺激素,共三次。各组大鼠于腹腔初次注射TAA始48h宰杀,取下腔静脉血检测FT_3、FT_4、TSH、rT_3及TB、ALT、AST等肝功能指标,取门静脉血测内毒素水平,取小肠组织测二胺氧化酶(DAO)活性,取小肠内容物及肠系膜淋巴结行细菌培养,取肝脏及末段回肠行普通HE染色观察,并使用图像分析系统测量小肠绒毛长度并行末段回肠壁内细胞间粘附因子I(ICAM-1)定量检测。
【结果】
1.与SO组比较,AHF组、AHF+TH组FT_3、FT_4降低(p＜0.01),rT_3升高(p＜0.01),TB、ALT、AST水平上升(p＜0.01),门静脉血浆内毒素水平显著升高(p＜0.01),小肠组织DAO活性下降(p＜0.01),小肠绒毛长度下降(p＜0.01),肠粘膜损伤评分增高(p＜0.01),小肠组织ICAM-1的表达水平升高(p＜0.01),肠系膜淋巴结细菌移位率增大(p＜0.01)。大鼠肠道4种正常菌数量均发生了显著性变化,其中肠杆菌、肠球菌数量明显上升(p＜0.01),双歧杆菌、乳酸杆菌数量显著下降(p＜0.01),出现肠道菌群失调。
2.AHF+TH组与AHF组比较,外周血FT_4升高(p＜0.01),FT_3升高(P＜0.05),rT_3降低(p＜0.01),ALT、AST、TB水平下降(p＜0.05),门静脉血浆内毒素水平降低(p＞0.05),小肠组织DAO活性升高(p＜0.05),小肠绒毛长度升高(p＜0.05),肠粘膜损伤程度降低(p＜0.05),肠系膜淋巴结细菌移位率及小肠组织ICAM-1的表达水平有所下降但无统计学意义(p＞0.05)。肠道各菌种变化较AHF组缓和,其中乳酸杆菌虽升高但无显著差异(p＞0.05),双歧杆菌有所升高(P＜0.05),肠杆菌、肠球菌下降(P＜0.05)。
【结论】急性肝衰竭时发生肠粘膜屏障的损害,且存在甲状腺激素代谢异常:FT_3、FT_4降低,rT_3升高。同时存在小肠组织二胺氧化酶(DAO)活性下降、门静脉血清内毒素水平升高、细菌移位等。补充外源性甲状腺激素有一定的保护肝脏功能和保护肠粘膜屏障的作用。
Objective:To investigate the injury of intestinal mucosa barrier,the metabolic abnormalities of thyroid hormone(TH),and the protective effect of exogenous thyroid hormone(TH) on intestinal mucosa barrier in rats with acute hepatic failure.
Methods:Thirty-four SD rats were randomly divided into three groups:ⅠSham group(SO group),N=10;ⅡAcute hepatic failure group(AHF group), N=12;ⅢAHF treated with thyroid hormone(AHF+TH group),N=12.The AHF Rat model(ⅡandⅢgroups) was created by repeated treatment of thioacetamide(TAA), 400mg/kg body weight(saline preparation 40mg/ml),by intraperitoneal injections at 0 and 24 hours.The rats in groupⅢ(AHF+TH group) were treated with three intraperitoneal thyroid hormome(TH) injections(15mg/kg) at-30 min,18 hours and 36 hours post TAA treaements.All rats were slaughtered at 48 hours after the initial TAA intraperitoneal injection,and underwent serum FT_3,FT_4,TSH,rT_3,endotoxin, TB,and ALT level measurements.The levels of diamine oxidase(DAO) and ICAM-1 expression in the intestine were measured.The bacteria in ileum and mesenteric lymph nodes were also cultured to observe the structural integrity of the intestinal mucosa.
Results:
1) GroupⅡ(AHF group) andⅢ(AHF+TH) were compared to the Sham group respectively.We found that the serum levels of FT_3,FT_4 and the activities of DAO were decreased(p＜0.01),whereas the serum levels of rT_3,TB,AST,ALT,endotoxin and ICAM-1 expressions in the intestine were increased(p＜0.01).The migration of Enterobacteriaceae and enterococci to the mesenteric lymph nodes were increased (p＜0.01).In contrast,the migration of lactobacillus and bifidobacteria to the same location were decreased(p＜0.01).As a result,this disrupted the balance of bacterial composition in the intestine.
2) When groupⅢ(AHF+TH group) was compared to groupⅡ(AHF),we found that the serum level of FT_3,FT_4 and the activities of DAO in the intestine were increased(p＜0.01/0.05) after thyroid hormone treatment in groupⅢ.In contrast,the serum level of rT_3,TB,ALT,AST were decreased(p＜0.01/0.05).The number of intestinal Enterobacteriaceae and enterococci were decreased(p＜0.05),whereas the number of lactobacillus and bifidobacteria were increased in the intestine.And the migration rate of bacteria to the mesenteric lymph nodes,endotoxin and ICAM-1 expressions in the intestine were decreased,although not significantly(p＞0.05). This showed the injury of intestinal mucosa barrier was lessened(p＜0.05)
Conclusion:Follow with the injure of intestinal mucosa barrier of acute hepatic failure,the level of FT_3,FT_4 and the activities of diamine oxidase were degraded,and the level of rT_3,the shifting rate of bacterium,endotoxin were increased.The supplement of exogenous thyroid hormone(TH) can protect intestinal mucosa barrier and the function of liver,and alleviate the injure of intestinal mucosa barrier in rats with acute hepatic failure.
【方法】SD大鼠34只,随机分为三组:①正常对照组(SO组)10只②急性肝衰竭组(AHF组)12只。③急性肝衰加甲状腺激素治疗组(AHF+TH组)12只。后两组大鼠按400mg/kg的标准腹腔内注射硫代乙酰胺(TAA),24h后用相同剂量TAA重复注射1次,模拟建立大鼠急性肝衰竭模型。AHF+TH组大鼠于造模前30min、首次腹腔注射TAA后18h、36h,分别按15μg·kg~(-1)的标准腹腔注射甲状腺激素,共三次。各组大鼠于腹腔初次注射TAA始48h宰杀,取下腔静脉血检测FT_3、FT_4、TSH、rT_3及TB、ALT、AST等肝功能指标,取门静脉血测内毒素水平,取小肠组织测二胺氧化酶(DAO)活性,取小肠内容物及肠系膜淋巴结行细菌培养,取肝脏及末段回肠行普通HE染色观察,并使用图像分析系统测量小肠绒毛长度并行末段回肠壁内细胞间粘附因子I(ICAM-1)定量检测。
【结果】
1.与SO组比较,AHF组、AHF+TH组FT_3、FT_4降低(p＜0.01),rT_3升高(p＜0.01),TB、ALT、AST水平上升(p＜0.01),门静脉血浆内毒素水平显著升高(p＜0.01),小肠组织DAO活性下降(p＜0.01),小肠绒毛长度下降(p＜0.01),肠粘膜损伤评分增高(p＜0.01),小肠组织ICAM-1的表达水平升高(p＜0.01),肠系膜淋巴结细菌移位率增大(p＜0.01)。大鼠肠道4种正常菌数量均发生了显著性变化,其中肠杆菌、肠球菌数量明显上升(p＜0.01),双歧杆菌、乳酸杆菌数量显著下降(p＜0.01),出现肠道菌群失调。
2.AHF+TH组与AHF组比较,外周血FT_4升高(p＜0.01),FT_3升高(P＜0.05),rT_3降低(p＜0.01),ALT、AST、TB水平下降(p＜0.05),门静脉血浆内毒素水平降低(p＞0.05),小肠组织DAO活性升高(p＜0.05),小肠绒毛长度升高(p＜0.05),肠粘膜损伤程度降低(p＜0.05),肠系膜淋巴结细菌移位率及小肠组织ICAM-1的表达水平有所下降但无统计学意义(p＞0.05)。肠道各菌种变化较AHF组缓和,其中乳酸杆菌虽升高但无显著差异(p＞0.05),双歧杆菌有所升高(P＜0.05),肠杆菌、肠球菌下降(P＜0.05)。
【结论】急性肝衰竭时发生肠粘膜屏障的损害,且存在甲状腺激素代谢异常:FT_3、FT_4降低,rT_3升高。同时存在小肠组织二胺氧化酶(DAO)活性下降、门静脉血清内毒素水平升高、细菌移位等。补充外源性甲状腺激素有一定的保护肝脏功能和保护肠粘膜屏障的作用。
Objective:To investigate the injury of intestinal mucosa barrier,the metabolic abnormalities of thyroid hormone(TH),and the protective effect of exogenous thyroid hormone(TH) on intestinal mucosa barrier in rats with acute hepatic failure.
Methods:Thirty-four SD rats were randomly divided into three groups:ⅠSham group(SO group),N=10;ⅡAcute hepatic failure group(AHF group), N=12;ⅢAHF treated with thyroid hormone(AHF+TH group),N=12.The AHF Rat model(ⅡandⅢgroups) was created by repeated treatment of thioacetamide(TAA), 400mg/kg body weight(saline preparation 40mg/ml),by intraperitoneal injections at 0 and 24 hours.The rats in groupⅢ(AHF+TH group) were treated with three intraperitoneal thyroid hormome(TH) injections(15mg/kg) at-30 min,18 hours and 36 hours post TAA treaements.All rats were slaughtered at 48 hours after the initial TAA intraperitoneal injection,and underwent serum FT_3,FT_4,TSH,rT_3,endotoxin, TB,and ALT level measurements.The levels of diamine oxidase(DAO) and ICAM-1 expression in the intestine were measured.The bacteria in ileum and mesenteric lymph nodes were also cultured to observe the structural integrity of the intestinal mucosa.
Results:
1) GroupⅡ(AHF group) andⅢ(AHF+TH) were compared to the Sham group respectively.We found that the serum levels of FT_3,FT_4 and the activities of DAO were decreased(p＜0.01),whereas the serum levels of rT_3,TB,AST,ALT,endotoxin and ICAM-1 expressions in the intestine were increased(p＜0.01).The migration of Enterobacteriaceae and enterococci to the mesenteric lymph nodes were increased (p＜0.01).In contrast,the migration of lactobacillus and bifidobacteria to the same location were decreased(p＜0.01).As a result,this disrupted the balance of bacterial composition in the intestine.
2) When groupⅢ(AHF+TH group) was compared to groupⅡ(AHF),we found that the serum level of FT_3,FT_4 and the activities of DAO in the intestine were increased(p＜0.01/0.05) after thyroid hormone treatment in groupⅢ.In contrast,the serum level of rT_3,TB,ALT,AST were decreased(p＜0.01/0.05).The number of intestinal Enterobacteriaceae and enterococci were decreased(p＜0.05),whereas the number of lactobacillus and bifidobacteria were increased in the intestine.And the migration rate of bacteria to the mesenteric lymph nodes,endotoxin and ICAM-1 expressions in the intestine were decreased,although not significantly(p＞0.05). This showed the injury of intestinal mucosa barrier was lessened(p＜0.05)
Conclusion:Follow with the injure of intestinal mucosa barrier of acute hepatic failure,the level of FT_3,FT_4 and the activities of diamine oxidase were degraded,and the level of rT_3,the shifting rate of bacterium,endotoxin were increased.The supplement of exogenous thyroid hormone(TH) can protect intestinal mucosa barrier and the function of liver,and alleviate the injure of intestinal mucosa barrier in rats with acute hepatic failure.
引文
[1]顾长海,王宇明.肝功能衰竭.第一版.重庆:人民卫生出版社.2002.3-4.
[2]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊疗指南[J].中华肝脏病杂志,2006,14(9):643-646.
[3]Hoke JB.Endotoxin and alcoholic liver disease:tolerance and susceptibility.Hepatology,1999,29:1602-1604.
[4]Ahamd N,GaHiner CR,Yurkow J,et al.Inhibition of macrophages with gadolinum chloridealters intercellular adhesion moleculare-1 expression in the liver during acute endotoxemia in rats.Hepatology,1999,29:728-736.
[5]石慧琳.应激对肠道屏障功能影响的研究进展.国外医学:消化系疾病分册,2003,23(3):164-167.
[6]韩德五.内毒素与肝功能不全.中国病理生理学杂志,1986,2:39.
[7]Chieveley-Willimas,Hamilton-Dvaies C.The role of the gut in major surgical post-operative morbidity.Int Anesthesiol Clin,1999,37(2):81-110.
[8]叶任高,陆再英等.内科学.第六版.北京:人民卫生出版社.2004.730-731.
[9]顾长海,王宇明.急性肝衰竭.第一版.四川成都:四川科学技术出版社.1997.141.
[10]高绪文,李继莲.甲状腺疾病.第一版.北京:人民卫生出版社.1999.16-18.
[11]黄耿文,杨连粤,杨建青等.甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用.中华实验外科杂志,2000,17(6):531-533.
[12]刘军桂.甲状腺素对肠缺血.再灌注肠粘膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2005.
[13]王志刚.甲状腺激素对大鼠阻塞性黄疸肠黏膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2006.
[14]Poison J,Lee WM.AASLD position paper:the management of acute liver failure[J].Hepatol,2005,41(5):1179-1197.
[15]Zimmermann C,Peter F,Christian P,et al.Hepatic encephalopathy in thioacetamide induced acute liver failure in rat:characterization of improved model and study of amino acidergic neurotransmission.Hepatology,1989,9(4):594.
[16]李兰娟,杨浓花,傅素珍.四种检测内毒素方法的比较[J].浙江医科大学学报,1992,21: 274-276.
[17]华静,李继强,曾民德等.双歧三联活菌对肝硬化患者肠道菌群的调节作用及其对内毒素血症的影响[J].中华消化杂志,2000,20(2):137-138.
[18]Deitch EA,Bridges RM.Effect of stress and trauma on bacterial translocation from the gut [J].J Surg Res,1987,42(5):536-542.
[19]Shou J,Lappin J,Minnard EA,et al.Total parenteral nutrition,bacterial translocation and host immune function[J].Am J Surg,1994,167:145-150.
[20]Ieuwenhuijzen GAP,Haskel Y,Lu Q,et al.Macrophage elimination increases bacterial translocation and gut origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation[J].Ann Surg,1993,218:791-799.
[21]黎君友,于燕,郝军等.分光光度法测定血和小肠组织二胺氧化酶活性[J].氨基酸和生物资源,1996,18(4):28-30.
[22]Lunn PG,Northrop-Clewes CA,Dowries RM.Intestinal permeability and growth fatering in Gamibian infants.Lancet,2003,338:907-910.
[23]Wang XD,Andersson R,Soltesz V,et al.Phospholipids prevent enteric bacterial translocation in the early stage of experimental acute liver failure in the rat.Scand J Gastroenterol,1994,29(12):1117.
[24]Wing XD,Deng XM,Haraldsen P,et al.Anti-oxidant and calcium channel blockers counter ace endothelial barrier injure by acute pancreatitis in rots.Scand J Gastroenterol,1995,30:1129-1136.
[25]杨连粤,黄耿文.外科危重病人正常甲状腺病态综合征的研究进展[J].中华实验外科杂志,2000,202:114-118.
[26]谢丹红.正常甲状腺病态综合征研究进展.新医学.2005,36(4):245-247.
[27]刘继海,杨连粤.甲状腺激素对脏器功能保护作用机制的研究进展.中国实用外科杂志,2001,21(6):372-276.
[28]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138-141.
[29]Moore FA.Role of gastrointestinal tract in the postinjury multiple organ failure.Am J Surg,1999,178(6):449.
[30]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138.
[31]Oren R,Sikuler E,Wong F,et al.The effects of hypothyroidism on liver status of cirrhotic patients[J].J Clin Gastroenterol,2000,31(2):162-163.
[32]Malik R,Hodgson H.The relationship between the thyroid gland and the liver[J].QJM,2002,95(9):559-569.
[33]Zietz B,Lock G,Plaeh B,et al.Dysfunetion of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis[J].Eur J Gastroenterol Hepatol,2003,15(5):495-501.
[34]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Phann Sci Technol Today,1999,2(7):281-287.
[35]韩德五等.肠源性内毒素血症与肝病-肝衰的IETM学说.第一版.北京:北京科学技术出版社,2004年.1-80.
[36]Lok GD.Plasma postheparin diamine oxidase.J Clin Invest,1997,71:1308-1315.
[37]方步武,邱奇,周振理等.急腹症内毒素血症期的全身性炎症反应.中国中西医结合外科杂志,2001,7(5):295-297.
[38]Schalch DS,Kalayoglu M,Pirsch JD,et al.Serum insulin-like growth factors and their binding proteins with hepatic failure and after liver transplantation.Metabolism,1998,47:200-206.
[39]Albrecht J,Hilgier W,Zielinska M,et al.Extracellular concentrations of taurine glutamate,and aspartate in the cerebral cortex of rats at the asymptomatic stage of thioacetamide-induced hepatic failurmodulation by ketamine anesthesia.Neurochem Res,2000,25(1):497-502.
[40]Assimakopulos SF,Vagianos CE,Patsoukis N,Georgiou C,Nikolopoulou V,Scopa CD,et al.Evidence for intestinal oxiadtive stress in obstructive jaundice-induced gut barrier dysfunction in rats.Acta Physiol Scand,2004,180(2):177-185.
[41]Wolochow H,Hidebrand GJ,Lammanna C.Translocation of microorganisms across the intestinal wall in rats:effect of microbial size and concentration[J].J Infect Dis,1996,116:523.
[42]Kasrvi FB,Wang LQ,Molin G,et al.Bacterial transloaction in acute liver injure induced by D-Galactosamine[J].Hepatology,1996,23:97-103.
[43]何效东,董家鸿.外科危重症与肠源性细菌/内毒素移位[J].中华胃肠外科杂志,2001,4(4):270-272.
[44]韩德五.肝功能衰竭发病机制的研究-肠源性内毒素血症假说.肝脏病杂志,1995;3(3):134-1373.
[45]王忠堂,姚咏明,肖光夏等.烫伤大鼠肠源性细菌移位危险性多因素分析[J].解放军医学杂志,2002,27:770-773.
[46]Staunton DE,Marlin SD,Stratowa C,et al.Primary structure of intercellular adhesion molecule-1(ICAM-1)demonstrates interaction between members of the immunoglobulin and integrin supergene families[J].Cell,1988,52:925-933.
[47]Albelda SM,Smith CW,Ward PA.Adhesion molecules and inflammatory injury[J].FASEB J,1994,8:504-512.
[48]Shields C J,Winter DC,Sookhai S,et al.Hypertonic saline attenuates end-organ damage in an experimental model of acute pancreatitis.Br J Surg,2000,87:1336-1340.
[49]朱春富,徐皓,陈小平等.淤血预处理对大鼠小肠淤血再灌注损伤的保护作用[J].南京医科大学学报(自然科学版),2008,28(4):513-517.
[1]顾长海,王宇明.肝功能衰竭.第一版.重庆:人民卫生出版社.2002.3-4.
[2]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊疗指南[J].中华肝脏病杂志,2006,14(9):643-646.
[3]叶任高,陆再英等.内科学.第六版.北京:人民卫生出版社.2004.730-731.
[4]高绪文,李继莲.甲状腺疾病.第一版.北京:人民卫生出版社.1999.16-18.
[5]杨连粤,黄耿文.外科危重病人正常甲状腺病态综合征的研究进展[J].中华实验外科杂志,2000,202:114-118.
[6]谢丹红.正常甲状腺病态综合征研究进展.新医学.2005,36(4):245-247.
[7]刘继海,杨连粤.甲状腺激素对脏器功能保护作用机制的研究进展.中国实用外科杂志,200121(6):372-276.
[8]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocytc marker.Surgery,1996,120(2):138-141.
[9]Oren R,Sikuler E,Wong F,et al.The effects of hypothyroidism on liver status of cirrhotic patients[J].J Clin Gastroenterol,2000,31(2):162-163.
[10]Malik R,Hodgson H.The relationship between the thyroid gland and the liver[J].QJM,2002,95(9):559-569.
[11]Zietz B,Lock G,Plach B,et al.Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis[J].Eur J Gastroenterol Hepatol,2003,15(5):495-501.
[12]何效东,董家鸿.外科危重症与肠源性细菌/内毒素移位[J].中华胃肠外科杂志,2001,4(4):270-272.
[13]韩德五等.肠源性内毒素血症与肝病-肝衰的IETM学说.第一版.北京:北京科学技术出版社,2004年.1-100.
[14]Moore FA.Role of gastrointestinal tract in the postinjury multiple organ failure.Am J Surg,1999,178(6):449.
[15]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138.
[16]黄耿文,杨连粤,杨建青等.甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用.中华实验外 科杂志,2000,17(6):531-533.
[17]刘军桂.甲状腺素对肠缺血-再灌注肠粘膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2005.
[18]王志刚.甲状腺激素对大鼠阻塞性黄疸肠黏膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2006.
[1]石慧琳.应激对肠道屏障功能影响的研究进展.国外医学:消化系疾病分册,2003,23(3):164-167.
[2]秦环龙,高志光.肠上皮细胞紧密连接在肠屏障中的作用研究进展.世界华人消化杂志2005;13(4):443-447.
[3]赵云平,陈惠孙,刘良明.内毒素移位与肠屏障功能不全.战创伤参考资料,1996;86(3):28-35.
[4]Dignass AU,Podolsky DK.Interleukin 2 modulates intestinal epithelial cell function in vitro.Exp Cell Res,1996;225(2):422-429.
[5]王浩,吴国豪.应激对肠屏障功能的影响.肠外与肠内营养,2002;9(2):123-127.
[6]Bevins CL,Martin-Porter E,Ganz T.Defensins and innate host defense of the gastrointestinal tract.Gut,1999;45(6):911-915.
[7]Ouellette AJ.Paneth cells and innate immunity in the crypt microenvironment.Gastroenterology,1997;113(5):1779-1784.
[8]Mark T,DeMeo,Ece A.Mutlu,Ali Keshavarzian,and Mary C.Tobin.Intestinal Permeation and Gastrointestinal Disease.J Clin Gastroenterol,2002;34(4):385-396.
[9]沈通一,秦环龙.谷氨酰胺对肠屏障功能保护作用的研究进展.肠外与肠内营养,2003;10(3):177-180.
[10]Trier JS.Structure and functional of intestinal M cell.Gastroenterol Clin Nor Am,1991;20(3):531-547.
[11]陈斌,许琰.肠道免疫与烧伤后肠细菌移位.医学综述,1998;4(12):12-14.
[19]薛光华.补充免疫球蛋白A防止细菌移位及维护肠上皮结构.国外医学·创伤与外科基本问题分册,1999;20(1):52-53.
[12]吴仲文,李兰娟,马伟杭,等.肠道微生物定植抗力的新指标—B/E值.浙江预防医学,2000;12(7):4-5.
[13]Berin MC,Kiliaan AJ,Yang PC,et al.The influence of mast cells on pathways of transepithelial antigen transport in rat intestine.J Immunol,1998;161(5):2561-2566.
[14]程君涛、肖光及、袁建成、秦孝建.腹内高压对免肠道通透性及内毒素细菌移位的影响.中华烧伤杂志,2003;19(4):229-232.
[15]罗力,侯明星.急性胰腺炎肠粘膜损伤情况及通透性改变的实验研究.内蒙古医学杂志, 2001;33(4):300-302.
[16]Zhao Hao,Li Xiao-ou,Lou Guo-qiang,et al.Research on intestinal permeability in patients with post-hepatitis cirrhosis.Chin J Infect Dis,2002;20(2):105-107.
[17]蔡元坤,秦新裕.D-乳酸与肠道屏障功能.国外医学外科学分册,2004;31(6):331-335.
[18]周殿元,潘令嘉.肠道菌群失调及治疗进展[J].胃肠病学,2001,6(4):2-3.
[19]Balzan,Silvio,deAlmeida Quadros,et al.Ivan Bacterial traaslocation:overview of mechanisms and clinical impact[J].Journal of Gastroenterology Hepatology,2007,22(4):464-471.
[20]陈亭苑,张思源.肠道细菌易位研究的进展.普外临床,1995,10(1):32-35.
[21]Coutinho H B,Robalinho T I,Coutinho A M,et al.Intra abdim inal sepsis:an immunocytochem ical study if the small intestine mucosa[J].J Clin Patho l,1997,50(4):294-298.
[22]Sanchez-Garcia M,Prieto A,Tejedor A,et al.Characteristics of thoracic ductlymph in multiple organ dysfunction syndrome[J].Arch Surg,1997,132:13-18.
[23]Gennari RA,lexander JW.Effects of hyperoxia on bacterial translocation and mortality during gut derived sepisis[J].Arch Surg,1996,131:57-62.
[24]Ieuwenhuijzen GAP,Haskel Y,Lu Q,et al.Macrophage elimination increases bacterial translocation and gut origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation[J].Ann Surg,1993,218:791-799.
[25]段美丽,王彦军,韩德五.急性肝功能衰竭时肠粘膜屏障损伤的研究[J].中国病理生理杂志.1999,15(10):906-908.
[26]Wing XD,Deng XM,Haraldsen P,et al.Anti-oxidant and calcium channel blockers counter ace endothelial barrier injury induced by acute pancreatitis in rats.Stand J Gastroenterol,1995,30:1129-36.
[27]吴承堂,黄祥成等.肠通透性增高与肠道细菌移位[J].世界华人消化杂志,1999,7(7):605-606.
[28]WANG XD,ANDERSSON AR,SOLTESZ V,et al.The influence of surgically induced acute liver failure on the intestine in the rat[J].Scand J Gastroenterol,1993,28:31-40.
[29]Sun ZW,Wang XD,Deng XM,et al.Beneficial effects of lexipafant,a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats.Dig Surg,2000,17:57-65.
[30]Mazzon E,Sautebin L,Caputi AP,et al.5-Lipoxygenase modulates the alteration of paracellu- lar barrier function in mice ileum during experimental colitis.Shock,2006,25:377-383.
[31]宋红丽,吕飒,刘沛.爆发性肝衰竭小鼠肠粘膜上皮细胞凋亡的研究.中国医科大学学报,2005,34(3):223-224.
[32]Gitter AH,Bendfeklt K,Sehulzke JD,et al.Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis[J].FASEB J.2000,14(12):1749-1753.
[33]韩德五.肠源性内毒素血症与肝病[M].北京:科学技术出版社,2004.
[34]Fox ES,Thomas P,Broitman SA,et al.Clearance of gut derived endotoxins by the liver.Release and modification of 3H,14C-lipopolysaccharide by isolated rat Kupffer cells.Gastroenterology,1989,96:456-461.
[35]Eberle D,Rachmilewitz D,Maitra S.Hepatocellular uptake and billary excretion of endotoxon.Gastroenterology,1980,79:1014.
[36]韩德五.肠源性内毒素血症与肝衰竭.临床肝胆病杂志,1996,12(1):50.
[37]刘立新,韩德五,马学惠.肠源性内毒素血症所致肝微循环障碍在肝损伤中的作用[J].中华传染病杂志,2001,19(2):94-96.
[38]Leigh HE,Lewis CC.Delta endotoxin is a potent inhibitor of the Na~+-K~+-ATP ase.J Biol Chem,1986,261:1170.
[39]王淑霞,于德顺,韩德五.硫代乙酰胺所致急性肝衰时内毒素血症与肝内胆汁淤积关系的研究.中国病理生理杂志,1997,13(6):674-676.
[40]张平.内毒素与肝脏损害.国外医学临床生物化学与检验学分册,1990,11(1):13.
[41]Beutler B,Milsark I W,Gerami AC.Passive immunization against cachectin/TNF protects mice from lethal effect of endotoxin.Science,1995,229:869.
[42]梁秀彬,乔中东,尹镭,等.内毒素体外诱导大鼠肝细胞凋亡[J].中华肝脏病杂志,1999,7(2):72-73.
[2]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊疗指南[J].中华肝脏病杂志,2006,14(9):643-646.
[3]Hoke JB.Endotoxin and alcoholic liver disease:tolerance and susceptibility.Hepatology,1999,29:1602-1604.
[4]Ahamd N,GaHiner CR,Yurkow J,et al.Inhibition of macrophages with gadolinum chloridealters intercellular adhesion moleculare-1 expression in the liver during acute endotoxemia in rats.Hepatology,1999,29:728-736.
[5]石慧琳.应激对肠道屏障功能影响的研究进展.国外医学:消化系疾病分册,2003,23(3):164-167.
[6]韩德五.内毒素与肝功能不全.中国病理生理学杂志,1986,2:39.
[7]Chieveley-Willimas,Hamilton-Dvaies C.The role of the gut in major surgical post-operative morbidity.Int Anesthesiol Clin,1999,37(2):81-110.
[8]叶任高,陆再英等.内科学.第六版.北京:人民卫生出版社.2004.730-731.
[9]顾长海,王宇明.急性肝衰竭.第一版.四川成都:四川科学技术出版社.1997.141.
[10]高绪文,李继莲.甲状腺疾病.第一版.北京:人民卫生出版社.1999.16-18.
[11]黄耿文,杨连粤,杨建青等.甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用.中华实验外科杂志,2000,17(6):531-533.
[12]刘军桂.甲状腺素对肠缺血.再灌注肠粘膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2005.
[13]王志刚.甲状腺激素对大鼠阻塞性黄疸肠黏膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2006.
[14]Poison J,Lee WM.AASLD position paper:the management of acute liver failure[J].Hepatol,2005,41(5):1179-1197.
[15]Zimmermann C,Peter F,Christian P,et al.Hepatic encephalopathy in thioacetamide induced acute liver failure in rat:characterization of improved model and study of amino acidergic neurotransmission.Hepatology,1989,9(4):594.
[16]李兰娟,杨浓花,傅素珍.四种检测内毒素方法的比较[J].浙江医科大学学报,1992,21: 274-276.
[17]华静,李继强,曾民德等.双歧三联活菌对肝硬化患者肠道菌群的调节作用及其对内毒素血症的影响[J].中华消化杂志,2000,20(2):137-138.
[18]Deitch EA,Bridges RM.Effect of stress and trauma on bacterial translocation from the gut [J].J Surg Res,1987,42(5):536-542.
[19]Shou J,Lappin J,Minnard EA,et al.Total parenteral nutrition,bacterial translocation and host immune function[J].Am J Surg,1994,167:145-150.
[20]Ieuwenhuijzen GAP,Haskel Y,Lu Q,et al.Macrophage elimination increases bacterial translocation and gut origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation[J].Ann Surg,1993,218:791-799.
[21]黎君友,于燕,郝军等.分光光度法测定血和小肠组织二胺氧化酶活性[J].氨基酸和生物资源,1996,18(4):28-30.
[22]Lunn PG,Northrop-Clewes CA,Dowries RM.Intestinal permeability and growth fatering in Gamibian infants.Lancet,2003,338:907-910.
[23]Wang XD,Andersson R,Soltesz V,et al.Phospholipids prevent enteric bacterial translocation in the early stage of experimental acute liver failure in the rat.Scand J Gastroenterol,1994,29(12):1117.
[24]Wing XD,Deng XM,Haraldsen P,et al.Anti-oxidant and calcium channel blockers counter ace endothelial barrier injure by acute pancreatitis in rots.Scand J Gastroenterol,1995,30:1129-1136.
[25]杨连粤,黄耿文.外科危重病人正常甲状腺病态综合征的研究进展[J].中华实验外科杂志,2000,202:114-118.
[26]谢丹红.正常甲状腺病态综合征研究进展.新医学.2005,36(4):245-247.
[27]刘继海,杨连粤.甲状腺激素对脏器功能保护作用机制的研究进展.中国实用外科杂志,2001,21(6):372-276.
[28]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138-141.
[29]Moore FA.Role of gastrointestinal tract in the postinjury multiple organ failure.Am J Surg,1999,178(6):449.
[30]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138.
[31]Oren R,Sikuler E,Wong F,et al.The effects of hypothyroidism on liver status of cirrhotic patients[J].J Clin Gastroenterol,2000,31(2):162-163.
[32]Malik R,Hodgson H.The relationship between the thyroid gland and the liver[J].QJM,2002,95(9):559-569.
[33]Zietz B,Lock G,Plaeh B,et al.Dysfunetion of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis[J].Eur J Gastroenterol Hepatol,2003,15(5):495-501.
[34]Daugherty AL,Mrsny RJ.Regulation of the intestinal epithelial paracellular barrier[J].Phann Sci Technol Today,1999,2(7):281-287.
[35]韩德五等.肠源性内毒素血症与肝病-肝衰的IETM学说.第一版.北京:北京科学技术出版社,2004年.1-80.
[36]Lok GD.Plasma postheparin diamine oxidase.J Clin Invest,1997,71:1308-1315.
[37]方步武,邱奇,周振理等.急腹症内毒素血症期的全身性炎症反应.中国中西医结合外科杂志,2001,7(5):295-297.
[38]Schalch DS,Kalayoglu M,Pirsch JD,et al.Serum insulin-like growth factors and their binding proteins with hepatic failure and after liver transplantation.Metabolism,1998,47:200-206.
[39]Albrecht J,Hilgier W,Zielinska M,et al.Extracellular concentrations of taurine glutamate,and aspartate in the cerebral cortex of rats at the asymptomatic stage of thioacetamide-induced hepatic failurmodulation by ketamine anesthesia.Neurochem Res,2000,25(1):497-502.
[40]Assimakopulos SF,Vagianos CE,Patsoukis N,Georgiou C,Nikolopoulou V,Scopa CD,et al.Evidence for intestinal oxiadtive stress in obstructive jaundice-induced gut barrier dysfunction in rats.Acta Physiol Scand,2004,180(2):177-185.
[41]Wolochow H,Hidebrand GJ,Lammanna C.Translocation of microorganisms across the intestinal wall in rats:effect of microbial size and concentration[J].J Infect Dis,1996,116:523.
[42]Kasrvi FB,Wang LQ,Molin G,et al.Bacterial transloaction in acute liver injure induced by D-Galactosamine[J].Hepatology,1996,23:97-103.
[43]何效东,董家鸿.外科危重症与肠源性细菌/内毒素移位[J].中华胃肠外科杂志,2001,4(4):270-272.
[44]韩德五.肝功能衰竭发病机制的研究-肠源性内毒素血症假说.肝脏病杂志,1995;3(3):134-1373.
[45]王忠堂,姚咏明,肖光夏等.烫伤大鼠肠源性细菌移位危险性多因素分析[J].解放军医学杂志,2002,27:770-773.
[46]Staunton DE,Marlin SD,Stratowa C,et al.Primary structure of intercellular adhesion molecule-1(ICAM-1)demonstrates interaction between members of the immunoglobulin and integrin supergene families[J].Cell,1988,52:925-933.
[47]Albelda SM,Smith CW,Ward PA.Adhesion molecules and inflammatory injury[J].FASEB J,1994,8:504-512.
[48]Shields C J,Winter DC,Sookhai S,et al.Hypertonic saline attenuates end-organ damage in an experimental model of acute pancreatitis.Br J Surg,2000,87:1336-1340.
[49]朱春富,徐皓,陈小平等.淤血预处理对大鼠小肠淤血再灌注损伤的保护作用[J].南京医科大学学报(自然科学版),2008,28(4):513-517.
[1]顾长海,王宇明.肝功能衰竭.第一版.重庆:人民卫生出版社.2002.3-4.
[2]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊疗指南[J].中华肝脏病杂志,2006,14(9):643-646.
[3]叶任高,陆再英等.内科学.第六版.北京:人民卫生出版社.2004.730-731.
[4]高绪文,李继莲.甲状腺疾病.第一版.北京:人民卫生出版社.1999.16-18.
[5]杨连粤,黄耿文.外科危重病人正常甲状腺病态综合征的研究进展[J].中华实验外科杂志,2000,202:114-118.
[6]谢丹红.正常甲状腺病态综合征研究进展.新医学.2005,36(4):245-247.
[7]刘继海,杨连粤.甲状腺激素对脏器功能保护作用机制的研究进展.中国实用外科杂志,200121(6):372-276.
[8]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocytc marker.Surgery,1996,120(2):138-141.
[9]Oren R,Sikuler E,Wong F,et al.The effects of hypothyroidism on liver status of cirrhotic patients[J].J Clin Gastroenterol,2000,31(2):162-163.
[10]Malik R,Hodgson H.The relationship between the thyroid gland and the liver[J].QJM,2002,95(9):559-569.
[11]Zietz B,Lock G,Plach B,et al.Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis[J].Eur J Gastroenterol Hepatol,2003,15(5):495-501.
[12]何效东,董家鸿.外科危重症与肠源性细菌/内毒素移位[J].中华胃肠外科杂志,2001,4(4):270-272.
[13]韩德五等.肠源性内毒素血症与肝病-肝衰的IETM学说.第一版.北京:北京科学技术出版社,2004年.1-100.
[14]Moore FA.Role of gastrointestinal tract in the postinjury multiple organ failure.Am J Surg,1999,178(6):449.
[15]Hodin RA,Shei A,Morin M,et al.Thyroid hormone and the gut:selective transcriptional activation of a villus-enterocyte marker.Surgery,1996,120(2):138.
[16]黄耿文,杨连粤,杨建青等.甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用.中华实验外 科杂志,2000,17(6):531-533.
[17]刘军桂.甲状腺素对肠缺血-再灌注肠粘膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2005.
[18]王志刚.甲状腺激素对大鼠阻塞性黄疸肠黏膜屏障功能的保护作用的学位论文.吉林延边:延边大学医学院,2006.
[1]石慧琳.应激对肠道屏障功能影响的研究进展.国外医学:消化系疾病分册,2003,23(3):164-167.
[2]秦环龙,高志光.肠上皮细胞紧密连接在肠屏障中的作用研究进展.世界华人消化杂志2005;13(4):443-447.
[3]赵云平,陈惠孙,刘良明.内毒素移位与肠屏障功能不全.战创伤参考资料,1996;86(3):28-35.
[4]Dignass AU,Podolsky DK.Interleukin 2 modulates intestinal epithelial cell function in vitro.Exp Cell Res,1996;225(2):422-429.
[5]王浩,吴国豪.应激对肠屏障功能的影响.肠外与肠内营养,2002;9(2):123-127.
[6]Bevins CL,Martin-Porter E,Ganz T.Defensins and innate host defense of the gastrointestinal tract.Gut,1999;45(6):911-915.
[7]Ouellette AJ.Paneth cells and innate immunity in the crypt microenvironment.Gastroenterology,1997;113(5):1779-1784.
[8]Mark T,DeMeo,Ece A.Mutlu,Ali Keshavarzian,and Mary C.Tobin.Intestinal Permeation and Gastrointestinal Disease.J Clin Gastroenterol,2002;34(4):385-396.
[9]沈通一,秦环龙.谷氨酰胺对肠屏障功能保护作用的研究进展.肠外与肠内营养,2003;10(3):177-180.
[10]Trier JS.Structure and functional of intestinal M cell.Gastroenterol Clin Nor Am,1991;20(3):531-547.
[11]陈斌,许琰.肠道免疫与烧伤后肠细菌移位.医学综述,1998;4(12):12-14.
[19]薛光华.补充免疫球蛋白A防止细菌移位及维护肠上皮结构.国外医学·创伤与外科基本问题分册,1999;20(1):52-53.
[12]吴仲文,李兰娟,马伟杭,等.肠道微生物定植抗力的新指标—B/E值.浙江预防医学,2000;12(7):4-5.
[13]Berin MC,Kiliaan AJ,Yang PC,et al.The influence of mast cells on pathways of transepithelial antigen transport in rat intestine.J Immunol,1998;161(5):2561-2566.
[14]程君涛、肖光及、袁建成、秦孝建.腹内高压对免肠道通透性及内毒素细菌移位的影响.中华烧伤杂志,2003;19(4):229-232.
[15]罗力,侯明星.急性胰腺炎肠粘膜损伤情况及通透性改变的实验研究.内蒙古医学杂志, 2001;33(4):300-302.
[16]Zhao Hao,Li Xiao-ou,Lou Guo-qiang,et al.Research on intestinal permeability in patients with post-hepatitis cirrhosis.Chin J Infect Dis,2002;20(2):105-107.
[17]蔡元坤,秦新裕.D-乳酸与肠道屏障功能.国外医学外科学分册,2004;31(6):331-335.
[18]周殿元,潘令嘉.肠道菌群失调及治疗进展[J].胃肠病学,2001,6(4):2-3.
[19]Balzan,Silvio,deAlmeida Quadros,et al.Ivan Bacterial traaslocation:overview of mechanisms and clinical impact[J].Journal of Gastroenterology Hepatology,2007,22(4):464-471.
[20]陈亭苑,张思源.肠道细菌易位研究的进展.普外临床,1995,10(1):32-35.
[21]Coutinho H B,Robalinho T I,Coutinho A M,et al.Intra abdim inal sepsis:an immunocytochem ical study if the small intestine mucosa[J].J Clin Patho l,1997,50(4):294-298.
[22]Sanchez-Garcia M,Prieto A,Tejedor A,et al.Characteristics of thoracic ductlymph in multiple organ dysfunction syndrome[J].Arch Surg,1997,132:13-18.
[23]Gennari RA,lexander JW.Effects of hyperoxia on bacterial translocation and mortality during gut derived sepisis[J].Arch Surg,1996,131:57-62.
[24]Ieuwenhuijzen GAP,Haskel Y,Lu Q,et al.Macrophage elimination increases bacterial translocation and gut origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation[J].Ann Surg,1993,218:791-799.
[25]段美丽,王彦军,韩德五.急性肝功能衰竭时肠粘膜屏障损伤的研究[J].中国病理生理杂志.1999,15(10):906-908.
[26]Wing XD,Deng XM,Haraldsen P,et al.Anti-oxidant and calcium channel blockers counter ace endothelial barrier injury induced by acute pancreatitis in rats.Stand J Gastroenterol,1995,30:1129-36.
[27]吴承堂,黄祥成等.肠通透性增高与肠道细菌移位[J].世界华人消化杂志,1999,7(7):605-606.
[28]WANG XD,ANDERSSON AR,SOLTESZ V,et al.The influence of surgically induced acute liver failure on the intestine in the rat[J].Scand J Gastroenterol,1993,28:31-40.
[29]Sun ZW,Wang XD,Deng XM,et al.Beneficial effects of lexipafant,a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats.Dig Surg,2000,17:57-65.
[30]Mazzon E,Sautebin L,Caputi AP,et al.5-Lipoxygenase modulates the alteration of paracellu- lar barrier function in mice ileum during experimental colitis.Shock,2006,25:377-383.
[31]宋红丽,吕飒,刘沛.爆发性肝衰竭小鼠肠粘膜上皮细胞凋亡的研究.中国医科大学学报,2005,34(3):223-224.
[32]Gitter AH,Bendfeklt K,Sehulzke JD,et al.Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis[J].FASEB J.2000,14(12):1749-1753.
[33]韩德五.肠源性内毒素血症与肝病[M].北京:科学技术出版社,2004.
[34]Fox ES,Thomas P,Broitman SA,et al.Clearance of gut derived endotoxins by the liver.Release and modification of 3H,14C-lipopolysaccharide by isolated rat Kupffer cells.Gastroenterology,1989,96:456-461.
[35]Eberle D,Rachmilewitz D,Maitra S.Hepatocellular uptake and billary excretion of endotoxon.Gastroenterology,1980,79:1014.
[36]韩德五.肠源性内毒素血症与肝衰竭.临床肝胆病杂志,1996,12(1):50.
[37]刘立新,韩德五,马学惠.肠源性内毒素血症所致肝微循环障碍在肝损伤中的作用[J].中华传染病杂志,2001,19(2):94-96.
[38]Leigh HE,Lewis CC.Delta endotoxin is a potent inhibitor of the Na~+-K~+-ATP ase.J Biol Chem,1986,261:1170.
[39]王淑霞,于德顺,韩德五.硫代乙酰胺所致急性肝衰时内毒素血症与肝内胆汁淤积关系的研究.中国病理生理杂志,1997,13(6):674-676.
[40]张平.内毒素与肝脏损害.国外医学临床生物化学与检验学分册,1990,11(1):13.
[41]Beutler B,Milsark I W,Gerami AC.Passive immunization against cachectin/TNF protects mice from lethal effect of endotoxin.Science,1995,229:869.
[42]梁秀彬,乔中东,尹镭,等.内毒素体外诱导大鼠肝细胞凋亡[J].中华肝脏病杂志,1999,7(2):72-73.