Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage.

OBJECTIVE: To examine the changes in the number of T cells and macrophages in the mucosal lamina propria in the presence or absence of bile in the gastrointestinal tract. DESIGN: Clinical study. SETTING: University hospital, Japan. SUBJECTS: 6 patients with obstructive jaundice who had external biliary drainage (drainage group) and 6 patients with no signs of obstructive jaundice (control group). INTERVENTIONS: Gastrointestinal specimens were taken at the time of operation. MAIN OUTCOME MEASURES: The number of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the lamina propria mucosae in each group measured immunohistochemically. RESULTS: The numbers of CD8 T cells and CD68+ macrophages in the lamina propria of the patients treated by external drainage were significantly less than in the control group (p < 0.01). However, there was no difference in the number of CD4+ T cells between the groups (p = 0.45). CONCLUSIONS: In the absence of bile, mucosal immune function fails as a result of reduced numbers of CD8+ T cells and macrophages.     

阻塞性黄疸时肠粘膜免疫功能变化的实验研究

阻塞性黄疸(阻黄)病人机体免疫功能受到抑制。本实验目的是研究阻黄时肠粘膜免疫功能的改变。实验包括阻黄组和对照组,采用胆总管结扎制造阻黄模型,以胆汁外引流组作为对照,每组15只动物。制造阻黄模型后2周,取小肠检测肠液中分泌型IgA(S-IgA)浓度、肠粘膜内淋巴细胞体外刺激转化能力、粘膜固有层内淋巴细胞亚群。结果显示:与对照组相比,阻黄鼠肠液S-IgA浓度降低;肠粘膜内淋巴细胞刺激转化能力降低;粘膜固有层内含IgA浆细胞、CD4阳性和CD8阳性淋巴细胞数目减少,差别有显著性(P>0.05)。因此,我们认为阻黄时肠粘膜免疫功能受到明显抑制。     

Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats

BACKGROUND: Our previous study using genetically labeled Escherichia coli strain JNW14 revealed that obstructive jaundice promotes bacterial translocation in rats and that the absence of bile in the intestinal tract is considered to be a factor inducing bacterial translocation. The aim of this study was to investigate the role of bile and bile acids in intestinal barrier function against bacterial translocation. MATERIALS AND METHODS: Eight-week-old male specific-pathogen-free Wistar rats were subjected to ligation of their common bile ducts (CBDL). The CBDL rats were treated with bacitracin, neomycin sulfate, and streptomycin sulfate, and the intestinal tract was colonized with E. coli strain JNW14, which was genetically labeled with resistant markers against the above three antibiotics, to monitor the bacterial translocation. The rats were then administered saline, cholic acid (20 mg/100 g BW), taurocholic acid (TCA: 5-50 mg/100 BW), or bile (1.5-6 mL/day) via a duodenal catheter. The degree of bacterial translocation of E. coli strain JNW14 to the mesenteric lymph nodes was compared. Histopathological examination of the terminal ileum and intestinal permeability test using phenolsulfonphthalein was also performed. RESULTS: Both cholic acid and TCA showed no inhibitory effect on bacterial translocation at any of the doses tested in CBDL rats, although TCA significantly decreased the numbers of E. coli strain JNW14 in the cecum. However, bile administration reduced the numbers of E. coli strain JNW14 in the cecum and mesenteric lymph nodes in CBDL rats although the inhibitory effect was weak. The integrity and permeability of the intestinal mucosa were kept at normal levels by bile administration in CBDL rats whereas the morphological changes, such as villous atrophy, villous edema, and lacteal canal dilatation, were observed in other CBDL rats. CONCLUSION: Bile plays an important role in maintaining the intestinal barrier function to prevent the invasion of enteric bacteria to the underlying tissues, suggesting that the intestinal administration of bile to patients with obstructive jaundice is a useful way to reduce infectious complications by inhibiting bacterial translocation from the intestine to other organs.     

Impaired Kupffer cell function and effect of immunotherapy in obstructive jaundice

BACKGROUND: Obstructive jaundice is frequently associated with septic complications. This study examined the influence of biliary obstruction on bacterial clearance and translocation. The study focused on the phagocytic and killing activities of Kupffer cells and the preventive effect on bacterial translocation of OK-432, which is a hemolytic streptococcal preparation developed as a biological response modifier. METHODS: To study the mechanism of sepsis in obstructive jaundice, two groups of Wistar rats were examined: rats subjected to common bile duct ligation (CBDL) and rats subjected to a sham operation. Bacterial clearance, organ distribution, hepatic blood flow, and phagocytic function of Kupffer cells were examined. To evaluate the effect of OK-432 on bacterial translocation, rats were divided into three groups: sham operation + phosphate-buffered saline (PBS), CBDL + PBS, and CBDL + OK-432. RESULTS: In this study, clearance of Escherichia coli. from the peripheral blood in CBDL rats was decreased significantly compared with that in sham-operated rats. Significant decreases in E.coli trapped in the liver and in hepatic blood flow were observed in CBDL rats compared with sham-operated rats. Phagocytic activity and superoxide production of Kupffer cells isolated from CBDL rats were significantly lower than in sham-operated rats. The incidence of bacterial translocation in CBDL rats was increased significantly, and oral administration of OK-432 prevented it. CONCLUSION: The results suggest that susceptibility to infection in obstructive jaundice is due to impaired phagocytic function of Kupffer cells. Furthermore, obstructive jaundice promotes bacterial translocation, and OK-432 may be useful in preventing this translocation.     

The Effect of Biliary Decompression on Bacterial Translocation in Jaundiced Rats

Patients with obstructive jaundice are prone to septic complications after biliary tract operations. Restoring bile flow to the intestine may help to decrease the complication rate. The present study is aimed at evaluating the effect of biliary decompression on bacterial translocation in jaundiced rats.Sixty-six male Sprague-Dawley rats were randomly allocated to six groups subjected to common bile duct ligation (CBDL) and transection (groups 2–6) or sham operation (group 1). In groups and 2 the incidence of enteric bacterial translocation was determined 2 weeks after sham operation or CBDL. In groups 3–6, biliary decompression was achieved by performing a choledochoduodenostomy after 2 weeks of biliary decompression. Bacterial translocation was then studied 1,2,3 and 5 weeks following biliary decompression.The rate of bacterial translocation to mesenteric lymph nodes in obstructive jaundice was significantly higher as compared with controls, and decreased with time to nil three weeks following biliary decompression. The incidence of bacterial translocation was closely correlated (r = 0.844; p = 0.034) with serum alkaline phosphatase activity and seemed to fit with the morphological changes noted in the small intestine. The decrease in bacterial translocation, however, lags behind the recovery of liver function as measured by routine liver function tests and antipyrine clearance.Obstructive jaundice thus promotes bacterial translocation in the rat. Biliary decompression gradually decreases the rate of bacterial translocation.     

中药黄芪对阻塞性黄疸大鼠细胞免疫功能的影响

目的 观察阻塞性黄疸大鼠细胞免疫功能的变化及中药黄芪对其细胞免疫功能的影响。方法：建立阻塞性黄疸大鼠模型，腹腔内注射黄芪（２５０ｍｇ／ｋｇ／ｄ）２周，测定血中Ｔ细胞表型ＣＤ３、ＣＤ４、ＣＤ８含量和血清白介素－２水平，并与对照组比较，结果 胆总管结扎３周后大鼠血中Ｔ细胞表型含量均有所下降，其中ＣＤ４减少相对更明显，血清 明显下降。腹腔注射黄苑２周可使大微ＣＤ３、ＣＤ４和ＣＤ８升高至接近正常，纠正ＩＬ     

Effect of FTY720 in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1

AIM: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mediates the homing of lymphocytes to gut-associated tissues (GALT). We performed a semiquantitative analysis of MAdCAM-1 expression during small bowel graft rejection in rat treated with FTY720. METHODS: Orthotopic small bowel transplantations (SBT) were performed from BN rats to LEW rats. Isografted animals served as controls. Three groups of SBT animals were studied on days 3, 5, 7 after operations (Isograft, untreated allograft, allograft with FTY720). FTY720 was orally administered by gavage (1 mg/kg/d) to allograft models on 7 consecutive days. Cryostat sections were prepared from grafts, including Peyer's patches (PPs). Indirect immunoperoxidase staining was performed using mAbs against MAdCAM-1. The degree of vascular endothelial staining on high endothelial venules (HEV) in the PPs was graded from 1 (low levels) to 5 (high levels), and in the vessels of the lamina propia from 1 (faint), to 2 (low at the base of villi), 3 (low to the middle of villi), 4 (high to the middle of villi), to 5 (high to villi tip). RESULTS: The graft survival was prolonged in the FTY720-treated group. MAdCAM-1 expression on HEVs in PPs was down-regulated during rejection. In contrast its expression on endothelial cells of vessels in the lamina propria was up-regulated during rejection. In the FTY720-treated groups, MAdCAM-1 expression on HEVs in PPs was up-regulated and its expression on endothelial cells of vessels in the lamina propria was down-regulated compared with untreated allograft group. CONCLUSIONS: Alteration in MAdCAM-1 expression may be associated with the development of SB graft rejection. The vessels at the base of villi, which are associated with lymphocyte recruitment, may become sites of intestine immune reactivity during the early phase of small bowel allograft rejection. FTY720 was found to prevent the down-regulation of MAdCAM-1 expression on HEVs in PPs and the up-regulation of its expression on endothelial cells of vessels in the lamina propria while also prolonging small bowel allograft survival.     

胆道梗阻及再通术后感染及与肠道细菌易位的关系

目的探讨胆道梗阻及再通后感染与肠道细菌易位的关系。方法分别对５１例胆道梗阻患者及３７例胆囊结石患者采用偶氮显色法测定门静脉血浆内毒素含量,同时行胆汁细菌培养及肠道菌群测定。结果胆道梗阻组肠道菌量及门静脉血浆内毒素含量较胆囊结石组明显升高（Ｐ＜０．０５）;此外,胆汁细菌培养５１例胆道梗阻患者中有４０例有菌生长（７８．４％）,与胆囊结石组（３２．４％）相比差异显著（Ｐ＜０．０１）。结论梗阻后胆道外引流及术后肠功能抑制均可诱发肠道细菌易位。胆道梗阻再通术后选用敏感抗生素行胆道冲洗,适当的胆道限流及促进胃肠蠕动,有助于维持胆道微生态环境的稳定,阻止肠源性内毒素入血,对防止肠道细菌易位,廓清术后胆道感染,改善预后具有非常重要的意义。     

胆道梗阻及再通术后感染与肠道细菌易位的关系

目的 探讨胆道梗阻及再通后感染与肠道细菌易位的关系。方法 分别对51例胆道梗阻患者及37例胆囊结石患者采用偶氮显色法测定门静脉血浆内毒素含量,同时行胆汁细菌培养及肠道菌群测定。结果 胆道梗阻组肠道菌量及门静脉血浆内毒素含量较胆囊结石组明显升高(P<0.05);此外,胆汁细菌培养51例胆道梗阻患者中有40例有菌生长(78.4%),与胆囊结石组(32.4%)相比差异显著(P<0.01)。结论 梗阻后胆道外引流及术后肠功能抑制均可诱发肠道细菌易位。胆道梗阻再通术后选用敏感抗生素行胆道冲洗,适当的胆道限流及促进胃肠蠕动,有助于维持胆道微生态环境的稳定,阻止肠源性内毒素入血,对防止肠道细菌易位,廓清术后胆道感染,改善预后具有非常重要的意义。     

Semiquantative analysis of expression of mucosal addressin cell adhesion molecule-1 during small bowel graft rejection in rats

AIM: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mediates the homing of lymphocytes to gut-associated lymphoid tissues (GALT). We performed a semiquantative analysis of MAdCAM-1 expression during small bowel graft rejection. METHODS: Orthotopic small bowel transplantations (SBT) were performed from BN rats to LEW rats. Isografted animals served as controls. Animals were sacrificed on days 3, 4, 5, 6, and 7 after SBT. Cryostat sections were prepared from grafts, including Peyer's patches (PPs). Indirect immunoperoxidase staining was performed using mAbs against MAdCAM-1. The degree of vascular endothelial staining on high endothelial venules (HEV) in the PPs was graded from 1 (low levels) to 5 (high levels), and in the vessels of the lamina propria from 1 (faint), 2 (low at the base of villi), 3 (low to the middle of villi), 4 (high to the middle of villi), to 5 (high to villus tip). RESULTS: MAdCAM-1 expression on HEVs in PPs was down-regulated during rejection. In contrast its expression on endothelial cells of vessels in the lamina propria was up-regulated during rejection. CONCLUSION: Alteration in MAdCAM-1 expression may be associated with the development of SB graft rejection. The vessels at the base of villi, which are associated with lymphocyte recruitment, may become sites of intense immune reactivity during the early phase of small bowel allograft rejection.     

Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

Effect of FTY720 and Ex Vivo Graft Irradiation in Rat Small Bowel Transplantation: Expression of Mucosal Addressin Cell Adhesion Molecule-1

Purpose We performed a semiquantitative analysis of the expression of Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and gut-associated tissues (GALT) during small bowel graft rejection in the rat to confirm the effect of FTY720 and ex vivo graft irradiation. Methods Small bowel transplantations (SBT) were performed from BN rats to LEW rats. Four groups of SBT animals were studied on days 3, 5, and 7 after operations (untreated, FTY720, ex vivo graft irradiation, FTY720+ex vivo graft irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The number of CD4-positive cells in the allografts was also analyzed by flow cytometry. Results The graft survival was prolonged only in the FTY720-treated groups. The SBT allografts treated by FTY720 demonstrated less infiltration, but the ex vivo graft irradiation group did not show any effect on its expression. In the FTY720-treated groups, MAdCAM-1 expression on high endothelial venules (HEVs) in Peyer's patches (PPs) was upregulated and its expression on endothelial cells of vessels in the lamina propria was downregulated in comparison with the allograft group without FTY720. Conclusions It is important to prevent the infiltration of CD4-positive cells, the downregulation of MAdCAM-1 expression on HEVs in PPs and the upregulation of MAdCAM-1 expression on endothelial cells of vessels in the lamina propria for the prolongation of graft survival.     

Effect of Bile Acid Replacement on Endotoxin-induced Tumor Necrosis Factor-a Production in Obstructive Jaundice

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-a) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-a production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-a levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-a levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-a production and intestinal bile acid replacement can inhibit this phenomenon.     

去氢胆酸钠治疗阻塞性黄疸内毒素血症的实验研究

目的:观察去氢胆酸钠降低阻塞性黄疸时血清内毒素的效果。方法:将CD大鼠随机分成对照组、胆总管结扎组和胆总管结扎-胆盐治疗组,测定各组血清胆红素、免疫球蛋白IgG、IgM和内毒素。结果:胆总管结扎-胆盐治疗组血清内毒素明显下降（P<0．01）,血清免疫球蛋白IgG、IgM有较明显升高。结论:口服去氢胆酸钠可能有助于降低阻塞性黄疸的血清内毒素。     

胆道梗阻时脱氧胆酸钠及乳果糖对小肠粘膜的影响

为观察外源性胆盐及乳果糖对小肠粘膜的影响，将２０只成年Ｗｉｓｔａｒ大鼠随机分为假手术组、胆管结扎组、胆管结扎＋胆盐治疗组和胆管结扎＋乳果糖治疗组，每组５只，２１天后处死动物，观察小肠粘膜的病理及四种酶活性的改变。结果：胆管结扎组小肠粘膜明显水肿，ＡＴＰａｓｅ、ＳＤＨ、ＡＫＰ活性明显减弱，Ａｃｐ活性明显增强；脱氧胆酸钠及乳果糖治疗组小肠粘膜未见异常或见轻度水肿，四种酶活性均较胆管结扎组有明显改善。提示，外源性胆盐及乳果糖对梗阻性黄疸时的小肠粘膜有保护作用。     

The effect of platelet activating factor antagonist BN 52021 on bacterial translocation and ICAM-I expression in experimental obstructive jaundice.

Expression of intracellular adhesion molecule-1 (ICAM-1) in an obstructive jaundice model and the potential protective role of platelet activating factor antagonist over small intestine and liver together with its effects on bacterial translocation are examined in this study. Forty-eight male Wistar albino rats were assigned into four equal groups of 12. In groups I and II, animals were sham operated. In groups III and IV, common bile duct ligation and division were performed. In group I and group III, 0.5 ml/day normal saline was applied intraperitoneally daily from day 2 to 6 of the study; in group II and group IV, 1 mg/kg/day BN 52021 was applied intraperitoneally daily from day 2 to 6 of the study. All animals were sacrificed on postoperative day 7. ICAM-1 expression (CD54 positivity) was analyzed in the liver and ileum tissue by immunohistochemical method. Samples from blood, liver mesenteric lymph nodes, and spleen were cultured under aerobic conditions. It is revealed that ICAM-1 expression was statistically higher in group III, with highest bacterial translocation and liver and spleen injury when compared to other groups. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (GGT), bilirubin, tumor necrosis factor alpha (TNFalpha), and interleukin 1beta(IL-1beta) values were at the highest level in group III, and there was a statistical decrease in group IV compared to group III. The administration of BN52021 in experimental obstructive jaundice is a useful way to reduce liver and intestinal mucosal villi damage by inhibiting bacterial translocation and systemic inflammatory response.     

胆汁回输联合早期肠内营养对良性梗阻性黄疸患者术后血清CRP及免疫功能的影响

目的 探讨胆汁回输联合早期肠内营养（early enteral nutrition,EEN）对良性梗阻性黄疸患者术后血清C反应蛋白（C-reactive protein,CRP）及免疫功能的影响.方法 将57例术后行胆汁外引流的良性梗阻性黄疸患者随机分为胆汁回输组（A组）、EEN组（B组）、胆汁回输联合早期肠内营养组（联合组,C组）,分别于术前1 d,术后第1、3、7天晨同一时间空腹抽取外周静脉血10 mL,测定CRP、C3、C4、IgA、IgM、IgG、T淋巴细胞亚群（CD3＋,CD4＋,CD8＋,CD4＋/CD8＋值）.观察患者病情转归情况,统计术后感染发生率.结果 联合组患者术后血清CRP水平低于EEN组及胆汁回输组（P＜0.05）.联合组与EEN组相比较,其T淋巴细胞功能恢复更迅速、恢复程度更高（P＜ 0.05）,免疫球蛋白及补体系统术后恢复较快（P＜0.05）;联合组与单纯胆汁回输组比较,两组术后免疫球蛋白及补体系统的恢复,在速度和程度上的差异不具有统计学意义（P＞ 0.05）.联合组术后感染发生率低于EEN组及胆汁回输组（P＜ 0.05）.结论 胆汁回输联合早期肠内营养能有效改善良性梗阻性黄疸患者的体液及细胞免疫功能,减轻术后炎症反应,降低术后感染发生率,促进术后快速康复.     

整合素α4β7的表达与溃疡性结肠炎大鼠肠淋巴细胞归巢

目的 探讨淋巴细胞归巢受体整合素α4β7的表达与溃疡性结肠炎(UC)大鼠肠淋巴细胞归巢的关系,分析UC大鼠肠道黏膜免疫功能改变的机制.方法 将40只SD大鼠随机分为UC组和对照组,分别于造模后72 h取标本检测:免疫组织化学法检测肠组织中地址素MAdCAM-1;逆转录-聚合酶链反应(RT-PCR)检测肠组织中α4β7的表达;流式细胞检测大鼠门静脉血中整合素α4阳性淋巴细胞数的变化.结果 UC组大鼠结肠黏膜下MAdCAM-1表达明显增强(0.72±0.33比0.21±0.41,P<0.01),主要表达在黏膜下微血管区;UC组α4、β7 mRNA的表达量与对照组比较明显升高(0.683±0.238;0.842±0.374比0.146±0.132;0.241±0.624,P均<0.01);UC组结肠静脉回流血中α4+淋巴细胞的比例明显高于对照组(76.73±8.24比14.66±6.74,P<0.01).结论 UC大鼠发病时α4β7阳性淋巴细胞的比例升高,参与肠淋巴细胞过渡归巢现象,肠黏膜免疫功能亢进可能是UC发病的重要因素.     

The effects of nitric oxide supplementation and inhibition on bacterial translocation in bile duct ligated rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. L-arginine or N(G)-nitro-L-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The L-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.     

The Effects of Nitric Oxide Supplementation and Inhibition on Bacterial Translocation in Bile Duct Ligated Rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, NG-nitro-¿-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. ¿-arginine or NG-nitro-¿-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The ¿-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.