胆道梗阻及再通术后ICAM-1表达变化的实验研究
|
摘要
目的：初步探讨SD大鼠胆道梗阻及再通术后细胞间粘附分子一1(ICAM—1)在外周血白细胞及肝脏和小肠组织中的表达变化及大鼠ICAM-1的异常表达与梗阻性黄疸器官功能损伤间的关系。
方法：随机将120只SD大鼠分成三组,手术对照组(SH)、梗阻性黄疸组(OJ)、胆肠内引流组(ID),第一次次手术SH组仅分离胆总管,OJ组、ID组行胆总管结扎,常规饲养7天之后二次开腹,SH组处理同前,OJ组仅分离胆总管,ID组行胆肠内引流术,于第一次手术后7天及第二次手术后1d、3d、7d不同时间点分别取标本,检测血清总胆红素(total bilirubin,TB)、谷丙转氨酶(alaninetransminase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)、白蛋白(Albumin.ALB)的含量。用流式细胞技术(flow cytometry,FCM)检测细胞间粘附分子—1(ICAM—1)在血、肝脏、肠道组织中的表达。用HE常规病理切片观察肝脏、肠道等组织病理学改变及免疫组织化学方法观察细胞间粘附分子一1(ICAM—1)在肝脏、肠道组织中的表达,对所得数据进行统计学处理。
结果：1、SD大鼠结扎胆总管后TB、ALT、AST等含量呈持续上升的变化,在结扎7天后达上升期高峰。结扎7天后OJ组、ID组与SH组各生化指标比较：均有统计学意义(P<0.05),表明胆道梗阻后7天各生化指标明显升高。ID组行胆肠内引流术后各生化指标明显下降,于术后7天左右恢复正常,OJ组未解除梗阻者持续处于高水平。两组不同时间相比较：P<0.05均有统计学意义,表明胆肠内引流后肝功能指标明显下降。
2、正常大鼠各组织细胞ICAM-1呈低表达水平,梗阻性黄疸7天后OJ组和ID组静脉血、肝及小肠组织细胞ICAM—1水平明显高于SH组,表明胆道梗阻后各组织ICAM-1呈明显上升趋势。ID组解除梗阻其表达明显下降,OJ组未解除梗阻者持续处于高水平,两组不同时间点比较P<0.05均有统计学意义,表明胆肠内引流后各组织ICAM-1表达明显下降。随着梗阻的时间延长,黄疽加重,各组比较更为显著；提示细胞间粘附分子一1(ICAM—1)与肝、肠组织损伤呈正相关。3、肝、肠组织病理变化：SH组肝脏病理显示正常肝小叶结构。OJ组胆管结扎后汇管区、小叶周边可见到新生小胆管样上皮细胞,少量炎性细胞浸润；原有肝内胆管上皮细胞有少量脱落现象并可见少量肝细胞的坏死灶。ID组内引流后病理变化逐渐恢复正常。OJ组未解除梗阻者胆管上皮细胞增生范围增大,细胞呈扁平形,管腔宽大,其外周基底膜及胶原纤维层增厚。偶有增生的胆管上皮细胞可分化成小胆管,增生的小胆管和纤维母细胞、胶原纤维形成间隔,分割、改建原有的肝小叶,使残存肝细胞形成大小不一的岛状结构。SH组大鼠肠黏膜完整,腺体形态完好,绒毛整齐而规则无萎缩性变化,未见细胞坏死等表现。OJ组肠黏膜在光镜下观察可发现肠粘膜萎缩,绒毛水肿,部分上皮细胞脱落,绒毛平均面积、高度、粘膜平均厚度均减少。随着梗阻时间的延长粘膜厚度变薄,绒毛变低、变窄、炎性细胞增多,小肠绒毛数量减少,变短变粗,互相融合,形态极不规则,并且存在绒毛断裂现象,肠腔内出现大小不等的绒毛碎片,小肠腺变短变细,成萎缩样变。ID组第二次手术后肠组织病理变化逐渐恢复正常。
结论：SD大鼠在通过结扎胆总管造成梗阻性黄疸时,其TB、ALT、AST变化的规律与人类不同,各生化指标水平在结扎胆总管术后第1-5天呈急剧上升趋势,第7天达到高峰,此后呈缓慢上升趋势,若梗阻未解除则持续处于高水平,若此时行胆肠内引流组各生化指标均明显下降,至术后第7天左右可降至正常。在梗阻性黄疽时ICAM—1参与了肝脏、肠道等组织的损伤,ICAM—1在肝脏、肠道组织中表达程度与血清总胆红素(TB)的水平呈正相关,表明ICAM—1的表达与黄疽的时间和水平程度密切相关；ICAM—1与ALT.AST变化呈正相关性,表明随着ICAM—1持续升高,组织损伤逐渐加重。这均说明血清ICAM
1的升高与器官功能障碍关系密切,其水平的高低极有可能反映OJ时组织损伤的严重程度。ICAM—1极有可能作为检测梗阻性黄疽(OJ)的重要指标。并提示尽早解除梗阻,可减轻组织损伤。
Objective:To investigate the changes of the expression of intercellular adhesion molecule 1 (ICAM—1) in WBC, liver, distal ileum of obstructive jaundice post-released in SD rats. And to assess relationship between the increased ICAM-1 expression and obstructive jaundice.
Methods:One hundred and twenty adult Sprague-Dawley rats were randomly assigned to three groups:sham operation(SH, n=40),obstructive jaundice(OJ, n=40) internal biliary drainage (ID, n=40). SH group, only the first separation surgery of common bile duct, OJ group, ID group underwent bile duct ligation. After seven days, A second surgery, SH groups to deal with the former, OJ group only isolated Common bile duct, ID group underwent biliary enteric drainage. On the 7th after the first operation and 1st,3 th,7th days after the second operation, the three groups were succumbed and the specimens of blood and liver, distal ileum were collected. The level of total bilirubin(TB), albumin (ALB), alanine transminase (ALT), aspartate aminotransferase (AST) in serum and liver, distal ileum tissue to value the result of the operation.The expression of ICAM-1 on WBC, liver, distal ileum tissue at different time points was detected by flow cytometry(FCM). HE conventional pathological section with the liver、intestine and other histopathological and immunohistochemical observation of intracellular adhesion molecule 1 (ICAM-1) in the liver, intestinal tissue, on the data for statistical analysis.
Results:1. The level of TB, ALT, AST,were rising and reaching the peak on the 7th day after the bile duct ligation. Ligation group and the SH group:P<0.05, were statistically significant, suggesting that the biochemical indicators increased significantly on the 7 days after biliary obstruction. The biochemical indices of ID group underwent biliary enteric drainage decreased significantly, and returned to normal on the 7 day after surgery. The biochemical indices of OJ group did not remove the obstruction, continuing high levels.The two groups at different times after the second operation compared:P<0.05 were statistically significant, and indicated that the biochemical decreased significantly after biliary enteric drainage.
2. The tissue cells of normal rats showed a low expression of ICAM-1 levels.The cell ICAM-1 levels were significantly higher than the SH group on the 7 days after the bile duct ligation. The ICAM-1of ID group underwent biliary enteric drainage decreased significantly. The ICAM-1of OJ group did not remove the obstruction, continuing high levels. The two groups at different times after the second operation compared:P <0.05 were statistically significant and indicated that the ICAM-1 decreased significantly after biliary enteric drainage.With the bile duct ligation prolonged the statistics is more significant; Prompted the ICAM-1 and liver, intestinal tissue injury was positively correlated
3.The pathological changes of liver、intestinal:SH group showed normal lobular architecture of liver pathology. On 7th day after bile duct ligation, new small biliary epithelia cells appeared in the portal areas and around the liver lobulars with some inflammatory cells infiltrated; As epithelial cells of intra-hepatic bile duct exfoliated some necrosis focuses of hepatic cells were being seen. Pathological changes of ID group gradually returned to normal after biliary enteric drainage. On 7th day after the second operation, in OJ group, the hyper-plastic areas of intra-hepatic bile duct epithelial cells enlarged, the cells were flat and the lumens of the bile ducts were wide, the basal membrane and collagen fibers layers thickened. Occasional ductular epithelial cells can be divided into small bile ducts, proliferation of small bile ducts and fibroblasts, collagen fibers interval, split, converted the original lobule, the remaining liver cells to form large or small island structure. The rats of SH group, intestinal mucosa, gland morphology intact, Hair neat and no atrophic changes in the rules and no tissue necrosis of the performance. OJ group of intestinal mucosa can be found in the intestinal mucosa under light microscope observation of atrophy, villous edema, some epithelial cells shed, the average area of hair, height, the average thickness of the mucosa were reduced. With time mucosal obstruction thinner hair goes low, narrow, inflammatory cells increased, reduce the number of intestinal villi, shorter thicker, convergence, form a very irregular. ID group after the second surgery the pathological changes of intestinal tissue gradually returned to normal.
Conclusion:By ligating the common bile duct causued the obstructive jaundice of SD rats.TB, ALT, AST, changes are different from humans. The level of TB, ALT, AST, were rising and reaching the peak on the 7th day after the bile duct ligation and then showed a slow upward trend. The biochemical indices of ID group underwent biliary enteric drainage decreased significantly, and returned to normal on the 7 day after surgery. The biochemical indices of OJ group did not remove the obstruction, continuing high levels.In obstructive jaundice, ICAM-1 cause the injury of liver、intestines and other tissue. The ICAM-1 of the liver、intestinal tissues and the levels of TB were positively correlated and suggested that the ICAM-1 have closely related with the time and level of obstructive jaundice; The leves of ICAM-1 and ALT, AST was positively correlated and indicated that with the ICAM-1 continued to rise, the aggravation of tissue injuryed. That all shows the increase of serum ICAM-1 is closely related with organ dysfunction, which can reflect the severity of tissue damage when the bile duct ligation. Detection of ICAM-1 can be used as an important indicator of obstructive jaundice (OJ) and suggested that early removed the Obstruction can reduced tissue damage.
方法：随机将120只SD大鼠分成三组,手术对照组(SH)、梗阻性黄疸组(OJ)、胆肠内引流组(ID),第一次次手术SH组仅分离胆总管,OJ组、ID组行胆总管结扎,常规饲养7天之后二次开腹,SH组处理同前,OJ组仅分离胆总管,ID组行胆肠内引流术,于第一次手术后7天及第二次手术后1d、3d、7d不同时间点分别取标本,检测血清总胆红素(total bilirubin,TB)、谷丙转氨酶(alaninetransminase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)、白蛋白(Albumin.ALB)的含量。用流式细胞技术(flow cytometry,FCM)检测细胞间粘附分子—1(ICAM—1)在血、肝脏、肠道组织中的表达。用HE常规病理切片观察肝脏、肠道等组织病理学改变及免疫组织化学方法观察细胞间粘附分子一1(ICAM—1)在肝脏、肠道组织中的表达,对所得数据进行统计学处理。
结果：1、SD大鼠结扎胆总管后TB、ALT、AST等含量呈持续上升的变化,在结扎7天后达上升期高峰。结扎7天后OJ组、ID组与SH组各生化指标比较：均有统计学意义(P<0.05),表明胆道梗阻后7天各生化指标明显升高。ID组行胆肠内引流术后各生化指标明显下降,于术后7天左右恢复正常,OJ组未解除梗阻者持续处于高水平。两组不同时间相比较：P<0.05均有统计学意义,表明胆肠内引流后肝功能指标明显下降。
2、正常大鼠各组织细胞ICAM-1呈低表达水平,梗阻性黄疸7天后OJ组和ID组静脉血、肝及小肠组织细胞ICAM—1水平明显高于SH组,表明胆道梗阻后各组织ICAM-1呈明显上升趋势。ID组解除梗阻其表达明显下降,OJ组未解除梗阻者持续处于高水平,两组不同时间点比较P<0.05均有统计学意义,表明胆肠内引流后各组织ICAM-1表达明显下降。随着梗阻的时间延长,黄疽加重,各组比较更为显著；提示细胞间粘附分子一1(ICAM—1)与肝、肠组织损伤呈正相关。3、肝、肠组织病理变化：SH组肝脏病理显示正常肝小叶结构。OJ组胆管结扎后汇管区、小叶周边可见到新生小胆管样上皮细胞,少量炎性细胞浸润；原有肝内胆管上皮细胞有少量脱落现象并可见少量肝细胞的坏死灶。ID组内引流后病理变化逐渐恢复正常。OJ组未解除梗阻者胆管上皮细胞增生范围增大,细胞呈扁平形,管腔宽大,其外周基底膜及胶原纤维层增厚。偶有增生的胆管上皮细胞可分化成小胆管,增生的小胆管和纤维母细胞、胶原纤维形成间隔,分割、改建原有的肝小叶,使残存肝细胞形成大小不一的岛状结构。SH组大鼠肠黏膜完整,腺体形态完好,绒毛整齐而规则无萎缩性变化,未见细胞坏死等表现。OJ组肠黏膜在光镜下观察可发现肠粘膜萎缩,绒毛水肿,部分上皮细胞脱落,绒毛平均面积、高度、粘膜平均厚度均减少。随着梗阻时间的延长粘膜厚度变薄,绒毛变低、变窄、炎性细胞增多,小肠绒毛数量减少,变短变粗,互相融合,形态极不规则,并且存在绒毛断裂现象,肠腔内出现大小不等的绒毛碎片,小肠腺变短变细,成萎缩样变。ID组第二次手术后肠组织病理变化逐渐恢复正常。
结论：SD大鼠在通过结扎胆总管造成梗阻性黄疸时,其TB、ALT、AST变化的规律与人类不同,各生化指标水平在结扎胆总管术后第1-5天呈急剧上升趋势,第7天达到高峰,此后呈缓慢上升趋势,若梗阻未解除则持续处于高水平,若此时行胆肠内引流组各生化指标均明显下降,至术后第7天左右可降至正常。在梗阻性黄疽时ICAM—1参与了肝脏、肠道等组织的损伤,ICAM—1在肝脏、肠道组织中表达程度与血清总胆红素(TB)的水平呈正相关,表明ICAM—1的表达与黄疽的时间和水平程度密切相关；ICAM—1与ALT.AST变化呈正相关性,表明随着ICAM—1持续升高,组织损伤逐渐加重。这均说明血清ICAM
1的升高与器官功能障碍关系密切,其水平的高低极有可能反映OJ时组织损伤的严重程度。ICAM—1极有可能作为检测梗阻性黄疽(OJ)的重要指标。并提示尽早解除梗阻,可减轻组织损伤。
Objective:To investigate the changes of the expression of intercellular adhesion molecule 1 (ICAM—1) in WBC, liver, distal ileum of obstructive jaundice post-released in SD rats. And to assess relationship between the increased ICAM-1 expression and obstructive jaundice.
Methods:One hundred and twenty adult Sprague-Dawley rats were randomly assigned to three groups:sham operation(SH, n=40),obstructive jaundice(OJ, n=40) internal biliary drainage (ID, n=40). SH group, only the first separation surgery of common bile duct, OJ group, ID group underwent bile duct ligation. After seven days, A second surgery, SH groups to deal with the former, OJ group only isolated Common bile duct, ID group underwent biliary enteric drainage. On the 7th after the first operation and 1st,3 th,7th days after the second operation, the three groups were succumbed and the specimens of blood and liver, distal ileum were collected. The level of total bilirubin(TB), albumin (ALB), alanine transminase (ALT), aspartate aminotransferase (AST) in serum and liver, distal ileum tissue to value the result of the operation.The expression of ICAM-1 on WBC, liver, distal ileum tissue at different time points was detected by flow cytometry(FCM). HE conventional pathological section with the liver、intestine and other histopathological and immunohistochemical observation of intracellular adhesion molecule 1 (ICAM-1) in the liver, intestinal tissue, on the data for statistical analysis.
Results:1. The level of TB, ALT, AST,were rising and reaching the peak on the 7th day after the bile duct ligation. Ligation group and the SH group:P<0.05, were statistically significant, suggesting that the biochemical indicators increased significantly on the 7 days after biliary obstruction. The biochemical indices of ID group underwent biliary enteric drainage decreased significantly, and returned to normal on the 7 day after surgery. The biochemical indices of OJ group did not remove the obstruction, continuing high levels.The two groups at different times after the second operation compared:P<0.05 were statistically significant, and indicated that the biochemical decreased significantly after biliary enteric drainage.
2. The tissue cells of normal rats showed a low expression of ICAM-1 levels.The cell ICAM-1 levels were significantly higher than the SH group on the 7 days after the bile duct ligation. The ICAM-1of ID group underwent biliary enteric drainage decreased significantly. The ICAM-1of OJ group did not remove the obstruction, continuing high levels. The two groups at different times after the second operation compared:P <0.05 were statistically significant and indicated that the ICAM-1 decreased significantly after biliary enteric drainage.With the bile duct ligation prolonged the statistics is more significant; Prompted the ICAM-1 and liver, intestinal tissue injury was positively correlated
3.The pathological changes of liver、intestinal:SH group showed normal lobular architecture of liver pathology. On 7th day after bile duct ligation, new small biliary epithelia cells appeared in the portal areas and around the liver lobulars with some inflammatory cells infiltrated; As epithelial cells of intra-hepatic bile duct exfoliated some necrosis focuses of hepatic cells were being seen. Pathological changes of ID group gradually returned to normal after biliary enteric drainage. On 7th day after the second operation, in OJ group, the hyper-plastic areas of intra-hepatic bile duct epithelial cells enlarged, the cells were flat and the lumens of the bile ducts were wide, the basal membrane and collagen fibers layers thickened. Occasional ductular epithelial cells can be divided into small bile ducts, proliferation of small bile ducts and fibroblasts, collagen fibers interval, split, converted the original lobule, the remaining liver cells to form large or small island structure. The rats of SH group, intestinal mucosa, gland morphology intact, Hair neat and no atrophic changes in the rules and no tissue necrosis of the performance. OJ group of intestinal mucosa can be found in the intestinal mucosa under light microscope observation of atrophy, villous edema, some epithelial cells shed, the average area of hair, height, the average thickness of the mucosa were reduced. With time mucosal obstruction thinner hair goes low, narrow, inflammatory cells increased, reduce the number of intestinal villi, shorter thicker, convergence, form a very irregular. ID group after the second surgery the pathological changes of intestinal tissue gradually returned to normal.
Conclusion:By ligating the common bile duct causued the obstructive jaundice of SD rats.TB, ALT, AST, changes are different from humans. The level of TB, ALT, AST, were rising and reaching the peak on the 7th day after the bile duct ligation and then showed a slow upward trend. The biochemical indices of ID group underwent biliary enteric drainage decreased significantly, and returned to normal on the 7 day after surgery. The biochemical indices of OJ group did not remove the obstruction, continuing high levels.In obstructive jaundice, ICAM-1 cause the injury of liver、intestines and other tissue. The ICAM-1 of the liver、intestinal tissues and the levels of TB were positively correlated and suggested that the ICAM-1 have closely related with the time and level of obstructive jaundice; The leves of ICAM-1 and ALT, AST was positively correlated and indicated that with the ICAM-1 continued to rise, the aggravation of tissue injuryed. That all shows the increase of serum ICAM-1 is closely related with organ dysfunction, which can reflect the severity of tissue damage when the bile duct ligation. Detection of ICAM-1 can be used as an important indicator of obstructive jaundice (OJ) and suggested that early removed the Obstruction can reduced tissue damage.
引文
[1]. Pitt HA, Cameron JL, Postier RG, Gadacz TR:Factors affecting mortality in biliary tract surgery. [J]Am J Surg 1981 141:66-72,
[2]. Su CH, Peng FK, LuiWY:Factors affectingmorbidity andmortality in biliary tract surgery. [J] World J Surg 1992,16:536-540,
[3].Pereira RM, dos Santos RA, Oliveira EA, et al. Development of hepatorenal syndrome in bile duct ligated rats. World J Gastroenterol 2008; 14:4505-4511
[4]. Li W, Chan A C W, Lau J Y W, et al. Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice:Effect of internal and external drainage. Journal of Gastroenterology and Hepatology,2004,19:160-165.
[5].Assimakopoulos S F, Thomopoulos K C, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest,2006, 36(3):181—187.]
[6]. Assimakopoulos S F, Vagianos C E, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand,2004,180:177-85.
[7]R rothlein, ML dustin, SD marin et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J]. Immunology,1986,137(4):1270-4
8. Tanabe D, Kamimoto Y, Kai M, et al. effects of biliary obstruction on the endocytic activity in hepatocyte and liver sinusoidal endothelial cells in rats. Rur Surg Res, 1996,28:201-209
[9]Zhang J S, Tan Y R, Xiang Y, et al Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB [J]. Acta Biochim Biophys Sin,2006, 38(2):119-128.
[10]Soehnlein O, Schmeisser A, Cicha I, et al. ACE inhibition lowers angiotensin-Ⅱ-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression [J]. Vase Res,2005,42 (5):399-407
[11]. Deitch EA, Sitting K, Berg R, Spegaw RD:Obstructive jaundice promotes bacterial translocation from the gut. Am J Surg 159:79-84,1990
[12]. BossuytHV, Desmaretz C, GaetaGB, Wisse E:The role of bile acids in the development of endotoxemia during obstructive jaundice in the rat. J Hepatol 10:274-279,1990
[13]. Sheen-Chen SM, Chau P, Harris HW:Obstructive jaundice alters Kupffer cell function independent of bacterial translocation. J Surg Res 1998,80:205-209,
[14]R rothlein, ML dustin, SD marin et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J].Immunology,1986,137 (4):1270-4
[15]Bendjelloul F, Rossmann P, Maly P, et al. Detection of 1CAM-I in experi-mentally induced colitis of ICAM-1 deficient and wild-type mice; an immune histochemical study. Histochem [J],2000,32:703-709.
[16]Mustjoki S, Alitalo R, Elonen E et al. Intercellular adhesion molecule-I inextravasation of normalmononuclear and leukaemia cells. Br J Haentartol,2001,113; 989-1000.
[17]黄洁夫,腹部外科学[M].北京：人民卫生出版社,2001：1082-1083
[18]罗琦,黄正接,阻塞性黄疽内毒素血症对肝组织血流肝能量代谢的影响[J].重庆医学,2001,30(2)：111-113
[19]刘立新,韩德五,肠源性内毒素血症与肝脏微循环障碍[J].中国微循环杂志2000,4(4)：251-252.
[20]赵宇,王金生,张文海,等.盐酸氟桂利嗪对鼠肝细胞钙超载的作用[J].中国医科大学学报,2000,29(5)：350-352
[21]. Fromowitz FB, Viola MY, Chao S, et al. Ras p21 expression in the progression of breast cancer. Hum Pathol,1987,18:1268~1275;
[22]林健,郑丽红,陈润,张荣标,医学动物防制2005年5月第21卷第5期321-322
[23]王茵楼正清来伟旗陈建国梅松龚幼菊,SD大鼠血液生化指标正常参考值范围的探讨[J]卫生毒理学杂志2006年6月第14卷第2期112-113
[24]Sano T, Ajiki T, Takeyama TY, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and ICAM-1 expression in jaundiced rats[J]. Surgery,2004,136(3);693-699.
[25]侯森林,乔占英,康建省,等.支架与手术引流对梗阻性黄疸患者免疫功能的影响[J].中华消化内镜杂志,2005,22(1)：46-47.
[26]孙杨忠,耿小平,阻塞性黄疸大鼠胆总管直径、压力及血清胆红素代谢变化的观察[J]肝胆外科杂志2003,2(11)：141-142.
[27]吴问汉,杨尹默,黄筵庭.梗阻性黄疽胆红素代谢的实验研究[J].中华肝胆外科杂志,2001,7(5)288-291.
[28]孙杨忠,耿小平,阻塞性黄疸大鼠胆总管直径、压力及血清胆红素代谢变化的观察[J],肝胆外科杂志,2003,11(2)：141-142.
[29]Ooi K, Soiraki K, Sakurai Y, et al. Clinical Significance of aboormal lipoprotein patterns in liver diseases[J]. Int J Mol Med,2005,15(4):655-660.
[30]Vassilice P, Filippou D, Manolis E, et al. Haenostessis impairment in patients with obstructive[J].J Gastrointestin liver Dis,2007,16 (2):178-186.
[31]Ogata Y, Nishi M, Nakayama H, et al. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats. [J]Surg Res,2003,115(1):18.
[32]Parks RW, Halliday MJ, MeCrory DC, et al.Hont inenune responsewith and intestinal permeahility in patients with jaundices [J].Br J Surg,2003, 90(2):239-245.
[33]Assimakopoulce SF, Vagiance CE, Charonis AS, et al. Experimental obsteuctive jaundice alters claudill-4 expression in intestinal mucosa:effect of bombesin and neurotensin [J]. World J Castroenterol,2006,12(21):3410-3415.
[34]Margaritis VG, Filos KS,Michalaki MA, et al. Effect of oral glutamine administration on bacterial tanslocation,endotoxemin,Liver and ileal morphology, and apoptosis in rats with obstructive jaundice[J]. World J Surg,2005,29 (10):1329-1334.
[35]Ogata Y,Nishi M, Nakayama H, et al.Role of bile in intestinal barrier function and its inhibitory effect on bactenal translocation in obstructive jaundice in rats[J].J Surg Res,2003,115 (1):18-23.
[36]2林木生,缪辉来.组织细胞间粘附分子-1在阻塞性黄疸小肠黏膜损伤中的作用及丹参防治机制的研究[J]中华实验外科杂志,2003,20(2)：130.
[37]Cuzzocrea S, Costantino G, Mazzon E, Micali A, et al. Beneficial effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion. [J] Pineal Res,2000,28(1):52.
[38]余永胜,潘沛思,侯英勇,等.细胞间粘附分于-1在乙型肝炎甲表达及意义[J]中华传染病杂志,1996.14(3)：134-136.
[39]张绪清,顾长海.乙型肝炎肝组织细胞间粘附分子—1表达[J]中华肝脏病杂志,1998,6(4)：206-207
[40]Eppihimer MJ, hipowsky HH. Effects of leukocyte-capillary plugging on the resistance to flow in the microvasculature of cremaster muscle for normal and activated leukocytes [J]. Microvas Res,1996,51 (2);187-201
[41]Monden K, Arii S, Ishiguro S, et al. Involuement of ICAM-1 expression on sinusoidal endothelial cell and neutrophil adherence in the reperfusion injury of cold-preserved livers[J].Transplant Proc,1995,27(1):759-761
[42]Hein 0 V, Misterek K, Tessmarm J P, et al. Time course of endothelial damage in septic shock:prediction of outcome[J]. Critical Care,2005,9(4):323—330.
[1]R ROTHLEIN, ML DUSTIN, SD MARIN et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J]. Immunology,1986,137(4):1270-4
[2]ZHANG J S, TAN Y R, XIANG Y, et al Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB[J]. Acta Biochim Biophys Sin,2006, 38(2):119-128.
[3]SOEHNLEIN O, SCHMEISSER A, CICHA I, et al. ACE inhibition lowers angiotensin-Ⅱ-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression [J]. Vase Res,2005,42 (5):399-407
[4]. VAN DER SAAG PT, CALDENHOVEN E, VAN DE STOLPE A, Molecular mechanisms of steroid action:a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors[J]. Eur Respir J Suppl.1996,8 (22) 146-153
[5]C. W. Park, J. H. Kim, J. W. Lee, et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent[J]. Diabetologia,2000:43(12):1544-1553
[6]AUDETTE M, LAROUCHE L, LUSSIER I, et al. Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells. [J].Eur Biochem,2001;268(6):1828-36
[7]CH JURGENSEN, BE HUBER, TP ZIMMERMAN et al.3-deazaadenosine inhibits leukocyte adhesion and ICAM-1 biosynthesis in tumor necrosis factor-stimulated human endothelial cells[J].Immunology,1990;144:Issue 2 653-661
[8]Hartwig W, Werner J, Warshaw AL,, et a.1 Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis [J]. Am J Physiol Gastrointest Liver Physiol 2004,287(6):G1194-G1199.
[9]RAMUDO L, DE DIOS I, YUBERO S, et a.l ICAM-1 and CDllb/CD18 expression during acute pancreatitis induced by bile-pancreatic duct obstruction:effect of N-acetylcysteine. J]. Exp Biol Med,2007,232(6):737-743.
[10]KA Roebuck, A Finnegan, Regulation of intercellular adhesion molecule-1 (CD54) gene expression[J].Leukocyte Biology,1999,Vol 66, Issue 6 876-888
[11]LNAN M, SAYEK 1, TEL BC, et al:Role of endotoxin and nitric oxide in the pathogenesisof renalfailure in obstructive jaundice[J]. Br J Surg,1997, 84(7):943-947.
[12]STELOS F, ASSIMAKOPOULOS, CONSTANTINE E. Intestinal failure in obstructive jaundice[J]. World J Gastroenterol,2005;11(24):3806-3807
[13]KUKUMA T, LEE Y, HIGA M, et al. Leptin, trglitazone, and the expression of sterl regulatory ele ment blinding proteins in liver and pancratic islets. Proc Nad. Acad Sci USA,2000,97 (15):8536-8541.
[14]MATTHIAS TSCHOP, DAVID L. SMILEY et al. Ghrlin induce adiposity in rodent[J]. Nature,2000.407 (6806):908-913.
[15]NEHEZ L, ANDERSSON R.Compromise of immune function in obstructive jaundice. [J]. Eur J Surg,2002,168(6):315-328.
[16]SINENCHENKO G I, KABANOV, MLU, TIKHONCHUK S V, Perspectives of using ozonized solutions in complex treatment of patients with mechanical jaundice [J]. Vestn Khir Im Ⅰ Ⅰ Grek,2004,163(3):91-94.
[17]DON ROCKEY, The cellular pathogenesis of portal hypertension:Stellate cell contractility, endothelin, and nitric oxide [J]. Hepatology,1997,25 (1):2-5.
[18]曹卫红,柴家科,胡森,等.肠道不全性缺血一再灌注损伤对远位免疫器官的影响[J].中华急诊医学杂志,2007,16(2)：176-179.
[19]]VAIL GRIENSVEN M, PROBST C, MULLER K, et al. Leukocyte-endothelialinteractiorm via ICAM-1 are detrimental in polymicmbial sepsis[J]. Shock,2006,25(3); 254-259
[2]. Su CH, Peng FK, LuiWY:Factors affectingmorbidity andmortality in biliary tract surgery. [J] World J Surg 1992,16:536-540,
[3].Pereira RM, dos Santos RA, Oliveira EA, et al. Development of hepatorenal syndrome in bile duct ligated rats. World J Gastroenterol 2008; 14:4505-4511
[4]. Li W, Chan A C W, Lau J Y W, et al. Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice:Effect of internal and external drainage. Journal of Gastroenterology and Hepatology,2004,19:160-165.
[5].Assimakopoulos S F, Thomopoulos K C, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest,2006, 36(3):181—187.]
[6]. Assimakopoulos S F, Vagianos C E, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand,2004,180:177-85.
[7]R rothlein, ML dustin, SD marin et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J]. Immunology,1986,137(4):1270-4
8. Tanabe D, Kamimoto Y, Kai M, et al. effects of biliary obstruction on the endocytic activity in hepatocyte and liver sinusoidal endothelial cells in rats. Rur Surg Res, 1996,28:201-209
[9]Zhang J S, Tan Y R, Xiang Y, et al Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB [J]. Acta Biochim Biophys Sin,2006, 38(2):119-128.
[10]Soehnlein O, Schmeisser A, Cicha I, et al. ACE inhibition lowers angiotensin-Ⅱ-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression [J]. Vase Res,2005,42 (5):399-407
[11]. Deitch EA, Sitting K, Berg R, Spegaw RD:Obstructive jaundice promotes bacterial translocation from the gut. Am J Surg 159:79-84,1990
[12]. BossuytHV, Desmaretz C, GaetaGB, Wisse E:The role of bile acids in the development of endotoxemia during obstructive jaundice in the rat. J Hepatol 10:274-279,1990
[13]. Sheen-Chen SM, Chau P, Harris HW:Obstructive jaundice alters Kupffer cell function independent of bacterial translocation. J Surg Res 1998,80:205-209,
[14]R rothlein, ML dustin, SD marin et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J].Immunology,1986,137 (4):1270-4
[15]Bendjelloul F, Rossmann P, Maly P, et al. Detection of 1CAM-I in experi-mentally induced colitis of ICAM-1 deficient and wild-type mice; an immune histochemical study. Histochem [J],2000,32:703-709.
[16]Mustjoki S, Alitalo R, Elonen E et al. Intercellular adhesion molecule-I inextravasation of normalmononuclear and leukaemia cells. Br J Haentartol,2001,113; 989-1000.
[17]黄洁夫,腹部外科学[M].北京：人民卫生出版社,2001：1082-1083
[18]罗琦,黄正接,阻塞性黄疽内毒素血症对肝组织血流肝能量代谢的影响[J].重庆医学,2001,30(2)：111-113
[19]刘立新,韩德五,肠源性内毒素血症与肝脏微循环障碍[J].中国微循环杂志2000,4(4)：251-252.
[20]赵宇,王金生,张文海,等.盐酸氟桂利嗪对鼠肝细胞钙超载的作用[J].中国医科大学学报,2000,29(5)：350-352
[21]. Fromowitz FB, Viola MY, Chao S, et al. Ras p21 expression in the progression of breast cancer. Hum Pathol,1987,18:1268~1275;
[22]林健,郑丽红,陈润,张荣标,医学动物防制2005年5月第21卷第5期321-322
[23]王茵楼正清来伟旗陈建国梅松龚幼菊,SD大鼠血液生化指标正常参考值范围的探讨[J]卫生毒理学杂志2006年6月第14卷第2期112-113
[24]Sano T, Ajiki T, Takeyama TY, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and ICAM-1 expression in jaundiced rats[J]. Surgery,2004,136(3);693-699.
[25]侯森林,乔占英,康建省,等.支架与手术引流对梗阻性黄疸患者免疫功能的影响[J].中华消化内镜杂志,2005,22(1)：46-47.
[26]孙杨忠,耿小平,阻塞性黄疸大鼠胆总管直径、压力及血清胆红素代谢变化的观察[J]肝胆外科杂志2003,2(11)：141-142.
[27]吴问汉,杨尹默,黄筵庭.梗阻性黄疽胆红素代谢的实验研究[J].中华肝胆外科杂志,2001,7(5)288-291.
[28]孙杨忠,耿小平,阻塞性黄疸大鼠胆总管直径、压力及血清胆红素代谢变化的观察[J],肝胆外科杂志,2003,11(2)：141-142.
[29]Ooi K, Soiraki K, Sakurai Y, et al. Clinical Significance of aboormal lipoprotein patterns in liver diseases[J]. Int J Mol Med,2005,15(4):655-660.
[30]Vassilice P, Filippou D, Manolis E, et al. Haenostessis impairment in patients with obstructive[J].J Gastrointestin liver Dis,2007,16 (2):178-186.
[31]Ogata Y, Nishi M, Nakayama H, et al. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats. [J]Surg Res,2003,115(1):18.
[32]Parks RW, Halliday MJ, MeCrory DC, et al.Hont inenune responsewith and intestinal permeahility in patients with jaundices [J].Br J Surg,2003, 90(2):239-245.
[33]Assimakopoulce SF, Vagiance CE, Charonis AS, et al. Experimental obsteuctive jaundice alters claudill-4 expression in intestinal mucosa:effect of bombesin and neurotensin [J]. World J Castroenterol,2006,12(21):3410-3415.
[34]Margaritis VG, Filos KS,Michalaki MA, et al. Effect of oral glutamine administration on bacterial tanslocation,endotoxemin,Liver and ileal morphology, and apoptosis in rats with obstructive jaundice[J]. World J Surg,2005,29 (10):1329-1334.
[35]Ogata Y,Nishi M, Nakayama H, et al.Role of bile in intestinal barrier function and its inhibitory effect on bactenal translocation in obstructive jaundice in rats[J].J Surg Res,2003,115 (1):18-23.
[36]2林木生,缪辉来.组织细胞间粘附分子-1在阻塞性黄疸小肠黏膜损伤中的作用及丹参防治机制的研究[J]中华实验外科杂志,2003,20(2)：130.
[37]Cuzzocrea S, Costantino G, Mazzon E, Micali A, et al. Beneficial effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion. [J] Pineal Res,2000,28(1):52.
[38]余永胜,潘沛思,侯英勇,等.细胞间粘附分于-1在乙型肝炎甲表达及意义[J]中华传染病杂志,1996.14(3)：134-136.
[39]张绪清,顾长海.乙型肝炎肝组织细胞间粘附分子—1表达[J]中华肝脏病杂志,1998,6(4)：206-207
[40]Eppihimer MJ, hipowsky HH. Effects of leukocyte-capillary plugging on the resistance to flow in the microvasculature of cremaster muscle for normal and activated leukocytes [J]. Microvas Res,1996,51 (2);187-201
[41]Monden K, Arii S, Ishiguro S, et al. Involuement of ICAM-1 expression on sinusoidal endothelial cell and neutrophil adherence in the reperfusion injury of cold-preserved livers[J].Transplant Proc,1995,27(1):759-761
[42]Hein 0 V, Misterek K, Tessmarm J P, et al. Time course of endothelial damage in septic shock:prediction of outcome[J]. Critical Care,2005,9(4):323—330.
[1]R ROTHLEIN, ML DUSTIN, SD MARIN et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J]. Immunology,1986,137(4):1270-4
[2]ZHANG J S, TAN Y R, XIANG Y, et al Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB[J]. Acta Biochim Biophys Sin,2006, 38(2):119-128.
[3]SOEHNLEIN O, SCHMEISSER A, CICHA I, et al. ACE inhibition lowers angiotensin-Ⅱ-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression [J]. Vase Res,2005,42 (5):399-407
[4]. VAN DER SAAG PT, CALDENHOVEN E, VAN DE STOLPE A, Molecular mechanisms of steroid action:a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors[J]. Eur Respir J Suppl.1996,8 (22) 146-153
[5]C. W. Park, J. H. Kim, J. W. Lee, et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent[J]. Diabetologia,2000:43(12):1544-1553
[6]AUDETTE M, LAROUCHE L, LUSSIER I, et al. Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells. [J].Eur Biochem,2001;268(6):1828-36
[7]CH JURGENSEN, BE HUBER, TP ZIMMERMAN et al.3-deazaadenosine inhibits leukocyte adhesion and ICAM-1 biosynthesis in tumor necrosis factor-stimulated human endothelial cells[J].Immunology,1990;144:Issue 2 653-661
[8]Hartwig W, Werner J, Warshaw AL,, et a.1 Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis [J]. Am J Physiol Gastrointest Liver Physiol 2004,287(6):G1194-G1199.
[9]RAMUDO L, DE DIOS I, YUBERO S, et a.l ICAM-1 and CDllb/CD18 expression during acute pancreatitis induced by bile-pancreatic duct obstruction:effect of N-acetylcysteine. J]. Exp Biol Med,2007,232(6):737-743.
[10]KA Roebuck, A Finnegan, Regulation of intercellular adhesion molecule-1 (CD54) gene expression[J].Leukocyte Biology,1999,Vol 66, Issue 6 876-888
[11]LNAN M, SAYEK 1, TEL BC, et al:Role of endotoxin and nitric oxide in the pathogenesisof renalfailure in obstructive jaundice[J]. Br J Surg,1997, 84(7):943-947.
[12]STELOS F, ASSIMAKOPOULOS, CONSTANTINE E. Intestinal failure in obstructive jaundice[J]. World J Gastroenterol,2005;11(24):3806-3807
[13]KUKUMA T, LEE Y, HIGA M, et al. Leptin, trglitazone, and the expression of sterl regulatory ele ment blinding proteins in liver and pancratic islets. Proc Nad. Acad Sci USA,2000,97 (15):8536-8541.
[14]MATTHIAS TSCHOP, DAVID L. SMILEY et al. Ghrlin induce adiposity in rodent[J]. Nature,2000.407 (6806):908-913.
[15]NEHEZ L, ANDERSSON R.Compromise of immune function in obstructive jaundice. [J]. Eur J Surg,2002,168(6):315-328.
[16]SINENCHENKO G I, KABANOV, MLU, TIKHONCHUK S V, Perspectives of using ozonized solutions in complex treatment of patients with mechanical jaundice [J]. Vestn Khir Im Ⅰ Ⅰ Grek,2004,163(3):91-94.
[17]DON ROCKEY, The cellular pathogenesis of portal hypertension:Stellate cell contractility, endothelin, and nitric oxide [J]. Hepatology,1997,25 (1):2-5.
[18]曹卫红,柴家科,胡森,等.肠道不全性缺血一再灌注损伤对远位免疫器官的影响[J].中华急诊医学杂志,2007,16(2)：176-179.
[19]]VAIL GRIENSVEN M, PROBST C, MULLER K, et al. Leukocyte-endothelialinteractiorm via ICAM-1 are detrimental in polymicmbial sepsis[J]. Shock,2006,25(3); 254-259