阻塞性黄疸时血清内毒素和肿瘤坏死因子的变化及相互关系

目的 :观察阻塞性黄疸发生时血清内毒素和TNF α的变化及相互关系。方法 :将大鼠随机分成对照组和胆总管结扎组 ,分别在第 3天、第 7天和第 2 1天测定血清内毒素和TNF α。结果 :胆总管结扎组的血清内毒素和TNF α逐渐升高 (P >0 .0 5 ,P <0 .0 5以及P <0 .0 1) ,两者相关系数为 0 .6 349(P <0 .0 0 1)。结论 :阻塞性黄疸发生时血清内毒素和TNF α明显升高 ,两者呈正相关     

阻塞性黄疸病人抗内毒素治疗的研究

目的 观察术前抗内毒素治疗对阻塞性黄疸病人内毒素血症的抑制作用。方法 阻塞性黄疸病人分三组在术前分别给予一般治疗（OJ组），口服胆盐（OJT1组）和静脉注射抗内毒素抗体（OJT2组），观察血浆内毒素（ET）及肿瘤坏死因子（TNF）含量变化。结果 三组术前ET和TNF水平无差异。OJT1和OJT2组用药后血浆ET水平均显著下降，明显低下OJ组（P＜0.01），术后进一步降低。OJT1和OJT2组术前和术后TNF水平与OJ组无明显差异。结论 术前应用胆盐和抗体可有效降低梗黄病人围手术期血浆ET水平。     

氢生理盐水对梗阻性黄疸大鼠肝功能的保护作用

目的研究氢生理盐水对梗阻性黄疸大鼠肝功能的保护作用并探讨其可能机制。方法将雄性SD大鼠随机分为3组(n=14),除假手术组外,均采用双重结扎胆总管造成阻黄模型,不同组大鼠分别给予等量生理盐水和氢生理盐水(5ml/kg,i.p.),10天后检测血清肝功能、内毒素及HMGB1水平,肝组织MDA、HMGB1、TNF-α、IL-1β、IL-6含量及MPO活性,并用光镜观察肝细胞变性、死亡和炎细胞浸润情况。结果胆总管结扎后,对照组大鼠肝功能水平明显降低,血清内毒素、HMGB1及肝组织MDA、HMGB1、TNF-α、IL-1β、IL-6含量及MPO活性明显升高,光镜下肝细胞大量变性坏死伴炎性细胞浸润。氢生理盐水治疗组大鼠肝功能显著好转,各指标明显低于对照组(P0.01)。结论氢生理盐水能显著减轻梗阻性黄疸大鼠肝损伤,并能有效抑制氧化应激及炎性反应。     

乳果糖、去氧胆酸钠和鹅去氧胆酸对阻塞性黄疸引起的内毒素血症的治疗对比研究

选用健康大白鼠３２只，制作４组阻塞性黄疸大白鼠模型、分别饲以一定量盐水、乳果糖、去氧胆酸钠和鹅去氧胆酸，然后观察大白鼠体静脉和门静脉血液的内毒素浓度以及血清胆红素含量。结果表明：乳果糖和去氧胆酸钠能同样程度地降低阻塞性黄疸大白鼠血液中内毒素浓度，但血清胆红素浓度没有变化。同时我们还发现，鹅去氧胆酸没有降低阻塞性黄疸大白鼠血液中内毒素的作用。     

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。     

神经病理性疼痛对溃疡性结肠炎大鼠肠道炎症变化及免疫球蛋白浓度的影响

目的观察脊神经结扎(spinal nerve ligation,SNL)导致的疼痛对溃疡性结肠炎大鼠肠道病理改变及循环中免疫球蛋白浓度的影响。方法健康雄性大鼠36只,体重200~220g,采用随机数字表法分为三组:SNL模型组(SNL组)、假手术组(Sham组)和对照组(Con组),每组12例。建立稳定的疼痛模型后,三组大鼠均予以三硝基苯磺酸(TNBS)诱导产生溃疡性结肠炎。分别于SNL术前、TNBS造模前及造模后第7天和第14天采血检测血清免疫球蛋白(IgG、IgM)浓度变化,并于造模后第7天取病变明显部位的结肠组织观察炎症病理改变。结果三组大鼠术前IgG、IgM浓度差异无统计学意义;脊神经结扎后SNL组血清IgG浓度略低于Sham组,而血清IgM浓度明显低于Sham组(P0.05);TNBS造模第7天SNL组大鼠血清IgG、IgM浓度升高幅度明显小于Sham组和Con组(P0.01);TNBS造模第14天SNL组大鼠血清IgG浓度明显低于Sham组及Con组(P0.05);TNBS造模第7天,与Sham组和Con组比较,SNI组结肠病变范围更为广泛,炎症程度更为严重。结论神经病理性疼痛抑制机体体液免疫,使血清IgM、IgG浓度降低,从而加重肠道炎症病理改变程度。     

乳果糖,去氧胆酸钠和鹅去氧胆酸对阻塞性黄疸引起的内毒素血…

选用健康大白鼠３２只，制作４组阻塞性黄疸大白鼠模型、分别饲以一定量盐水、乳果糖、去氧胆酸钠和鹅去氧胆酸，然后观察大白鼠体静脉和门静脉血液的内毒素浓度以及血清胆红素含量。结果表明：乳果糖和去氧胆酸钠 样程度地降低阻塞性黄疸大白鼠血液中内毒素浓度，但血清胆红素浓度没有变化。同时我们还发现，鹅去氧胆酸没有降低阻塞性黄疸大白鼠血液中内毒素的作用。     

梗阻性黄疸时内毒素血症对肾功能的影响及胆酸钠、乳果糖和山莨菪碱的干预效应

目的 观察梗阻性黄疸患者手术前后血中内毒素含量、肾功能变化及胆酸钠、乳果糖和山莨菪碱的干预效应。方法 将48例梗阻性黄疸患者随机分为对照组（n=15）,胆酸钠治疗组（n=11）,乳果糖治疗组（n=10）,山莨菪碱治疗组（n=12）;另选21例胆囊结石患者为非梗阻性黄疸对照组。观察各组手术前后血中内毒素含量、肾功能变化及药物治疗后的变化。结果 梗阻性黄疸时血中内毒素水平明显升高,内生肌酐清除率明显下降,各治疗组血中内毒素水平下降,内生肌酐清除率上升。结论 梗阻性黄疸时肠源性内毒素是导致肾功能损害的重要原因。胆酸钠、服果糖和山莨菪碱可降低血中内毒素水平,对肾功能有保护作用。     

肝外良性阻塞性黄疸术后消化道出血55例分析

目的: 研究肝外良性阻塞性黄疸与消化道出血之间的关系及其防治措施. 方法: 对因肝外良性阻塞性黄疸行胆总管切开引流术等后而发生消化道出血的55例患者进行分析. 结果: 阻塞性黄疸所致的高胆红素血症,内毒素和胆盐的作用,及术后禁食时间过长等为引起消化道出血的主要因素. 结论: 术后早期进食,改善微循环、止酸剂及应用胃粘膜保护剂、补充维生素K,有助于消化道出血的预防及治疗.     

阻塞性黄疸大鼠法尼酯衍生物X受体表达及加味大柴胡汤作用的研究

目的:研究法尼酯衍生物X受体(FXR)对胆汁酸代谢的作用,以及加味大柴胡汤对FXR的表达的影响.方法:制作急性阻塞性黄疸大鼠模型,分为7、14、21 d 3个时段,每个时段又分为胆总管结扎 加味大柴胡汤组、胆总管结扎 TUDCA、胆总管结扎组 生理盐水组、假手术 生理盐水组等4组,每组6只.生化检测ALT、TB、TBA、ALP;免疫组化法检测FXR蛋白表达.结果:胆道梗阻后,随梗阻时间的延长,FXR表达减弱.血清TBA、ALT、ALP、TB含量明显增加.加味大柴胡汤使FXR表达上调,血清TBA、ALT、ALP、TB明显下降,肝脏病变减轻.结论:阻塞性黄疸时FXR表达可调节胆汁酸代谢.加味大柴胡汤可以上调FXR蛋白表达,促进胆汁酸代谢,从而减轻肝脏损害.     

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.     

Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats

BACKGROUND: Although the effect of preoperative biliary drainage in patients with obstructive jaundice is controversial, bacterial or endotoxin translocation is one of the main postoperative problem in jaundiced patients. Failure in gut barrier functions causes bacterial translocation; homing and distribution of T lymphocytes in the intestinal lamina propria are important for gut mucosal immune defense. This study was performed to examine whether bile regulates the numbers of T lymphocyte subsets or the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in experimental jaundice in rats with and without external and internal biliary drainage. METHODS: Four groups of Wistar rats were used: those that received a sham operation (SHAM), common bile duct ligation (CBDL), CBDL followed by external drainage (ED), and CBDL followed by internal drainage (ID). Numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria were counted immunohistochemically in the specimens of jejunum and ileum of each group. Bacterial translocation was examined by culturing from the mesenteric lymph node complex isolated from rats in each group. RESULTS: A significant decrease in numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria was seen in obstructive jaundice, although numbers of peripheral blood lymphocytes increased in comparison with the sham-operated control. The numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1 expression in the lamina propria did not recover to a normal level after external drainage, but did so after internal drainage. Frequencies of bacterial translocation were high in the CBDL and ED group. In contrast, bacterial translocation was not present in any animals in the SHAM group and was at a low percentage in the ID group. CONCLUSIONS: Changes in the number of T lymphocytes and MAdCAM-1 expression are associated with the presence of bile in the gastrointestinal tract and are inversely correlated with the frequency of bacterial translocation induced by CBD ligation. MAdCAM-1 expression maintained by the presence of bile may regulate T-lymphocyte homing to the lamina propria in obstructive jaundice.     

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.     

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.     

胆汁转流性外引流术对恶性梗阻性黄疸血内毒素水平的影响

目的 :探讨外引流术体外转流胆汁对恶性梗阻性黄疸病人血内毒素水平的影响。方法 :对 14例肿瘤手术不能切除的恶性梗阻性黄疸病人行胆汁转流性外引流术 ,与同期施行的 15例内引流术、2 0例外引流术病人进行手术前后外周血内毒素水平比较。结果 :术前 3组内毒素水平差别无显著性意义 (P>0 .0 5 )。单纯外引流组手术后内毒素水平略高于术前 (P >0 .0 5 ) ;内引流组术后第 2天内毒素水平反而高于术前 (P <0 .0 5 ) ,第 7天、第 14天显著降低 (P <0 .0 5 ,P <0 .0 1) ;体外转流组术后内毒素水平逐渐降低 ,与内引流术组变化基本相同。结论 :胆汁转流性外引流术可降低恶性梗阻性黄疸病人外周血内毒素水平。     

Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis.

OBJECTIVE: To elucidate the time course of endotoxaemia and antiendotoxin antibodies in patients with acute pancreatitis. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. SUBJECTS: 25 patients with oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls. MAIN OUTCOME MEASURES: Concentrations of endotoxin and immunoglobulins (classes G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day period. RESULTS: There were no differences in the degree of endotoxaemia between patients with oedematous and necrotising pancreatitis on admission. However, from the day after admission and throughout the observation period patients with necrotising pancreatitis had significantly higher concentrations of endotoxin than those with oedematous pancreatitis. Concentrations of IgM specific for endotoxin peaked at day 4, and then decreased in patients with oedematous pancreatitis while remaining high for those with necrotising pancreatitis. There was only a slight increase in IgA specific for endotoxin, and IgG and immunoglobulins to gamma-haemolysin remained steady throughout the observation period. There was strong cross-reactivity (r > 0.7) between IgM specific for endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS: Necrotising pancreatitis is accompanied by persistent endotoxaemia with an extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis have a transient endotoxaemia with a temporary increase of Ig specific for endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM) despite general immunosuppression.     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.

Abstract：

Objective To evaluate the therapeutic effect and mechanism of specific inducible nitric oxide synthase(iNOS)aminoguanidine(AG)in rats with obstructive jaundice.Methods Forty male Wistar rats were divided randomly into four groups: normal control group, sham operation group, obstructive jaundice group and aminoguanidine therapeutic group.Each group had 10 rats.We assayed levels of liver function,hemobilirubin, endotoxin,lactic acid and malondialdehyde before and after therapy, and we also analyzed pathology of the liver and small intestine.Then we could explore the therapeutic effect of AG in rats with obstructive jaundice.Results The levels of endotoxin,lactic acid and malondialdehyde in blood increased progressively along with the pathological changes of the liver and small intestine.Each of the AG group parameters was significantly lower, and the pathological changes of liver and small intestine were improved.Conclusion AG could protect liver and small intestine by attenuating lipid peroxidative and endotoxemia,and provide a new way to cure obstructive jaundice.     

梗阻性黄疸兔血浆内毒素和内皮素1含量与血流动力学改变的关系

研究梗阻性黄疸内毒素血症对血管内皮细胞产生内皮素１（ＥＴ－１）的作用及ＥＴ－１与梗阻性黄应时血流动力学改变的关系。方法用肝总管结扎法建立梗阻性黄疸（ＯＪ）兔模型,偶氮显色法定量测定血内毒素含量,特异性放射免疫分析法测定血浆ＥＴ－１,生理记录仪和电磁血流计测定心率（ＨＲ）、平均动脉压（ＭＡＰ）、心输出量（ＣＯ）、肝动脉血流量（ＨＡＢＦ）、门静脉血流量（ＰＶＢＦ）、门静脉压力（ＰＶＰ）及内脏血管阻力（ＳＡＲ）。结果ＯＪ组血浆内毒素含量明显高于正常对照（ＮＣ）组;血浆ＥＴ－１低于ＮＣ组。ＯＪ组血浆内毒素与血浆ＥＴ－１含量呈负相关;ＯＪ组血浆ＥＴ－１含量与ＭＡＰ、ＨＡＢＦ、ＰＶＢＦ及ＳＡＲ呈正相关。结论梗阻性黄疽时血浆ＥＴ－１水平降低,内毒素血症不能刺激血管内皮细胞产生ＥＴ－１,血浆ＥＴ－１水平下降在系统血流动力学改变中起一定的作用。