Effect of honey on bacterial translocation and intestinal morphology in obstructive jaundice

AIM：To evaluate the effects of honey on bacterial translocation and intestinal villus histopathology in experimental obstructive jaundice.
METHODS：Thirty Wistar-Albino rats were randomly divided into three groups each including 10 animals：group Ⅰ,sham-operated;group Ⅱ,ligation and section of the common bile duct（BDL）;group Ⅲ,bile duct ligation followed by oral supplementation of honey（BDL＋honey） 10 g/kg per day.Liver,blood,spleen,mesenteric lymph nodes,and ileal samples were taken for microbiological,light and transmission electrone microscopic examination.
RESULTS：Although the number of villi per centimeter and the height of the mucosa were higher in sham group,there was no statistically significant difference between sham and BDL ＋ honey groups（P〉0.05）.On the other hand,there was a statistically significant difference between BDL group and other groups（P〈0.05）.The electron microscopic changes werealso different between these groups.Sham and honey groups had similar incidence of bacterial translocation（P〉0.05）.BDL group had significantly higher rates of bacterial translocation as compared with sham and honey groups.Bacterial translocation was predominantly detected in mesenteric lymph nodes.
CONCLUSION：Supplementation of honey in presence of obstructive jaundice ameliorates bacterial translocation and improves ileal morphology.     

Obstructive jaundice promotes intestinal-barrier dysfunction and bacterial translocation: experimental study

Background Although clinical and experimental studies have demonstrated a correlation between obstructive jaundice and the development of sepsis, the mechanism has not been fully elucidated. Purpose The aim of this study was to investigate the influence of biliary obstruction on bacterial translocation as a possible source of infection in cases of obstructive jaundice. Material and Methods Two groups of 12 Wistar rats were examined: rats subjected to common bile duct (CBD) ligation (group A) and rats subjected to a sham operation (group B). After 7 days, blood samples were taken and liver, spleen, and mesenteric lymph nodes (MLNs) from the ileocecal area were removed, divided into small pieces, and cultured. Quantitative culture results were determined by the number of colony-forming units (CFU) per milliliter of homogenate. Bacterial translocation was defined as the presence of a positive culture of MLNs, blood, liver, and/or spleen. Samples for histopathological examination were taken from the mucosa of the ileum and the colon and evaluated for inflammatory and destructive changes. Results There was no evidence of bacterial translocation to MLNs, blood, spleen, or liver detected in any of the 12 sham-operated control rats. In contrast, bacterial translocation was demonstrated in 8 of the 12 CBD-ligated rats (P < 0.01). In all eight cases in which translocation occurred, Escherichia coli were cultured from the MLNs. There were no histological changes in the mucosal samples of the control animals. In the CBD-ligated rats, hyperemia, vacuolization, reduction of goblet cells, decreased mitotic activity, and infiltration by lymphocytes and polymorphonuclear leukocytes (PMNLs) were detected. Cases in which translocation occurred were significantly associated with decreased mitotic activity in the colon (r = −0.5, P < 0.01) and higher infiltration by PMNLs in the ileum (r = −0.62, P < 0.05). Conclusion Obstructive jaundice in a rat model predisposes to bacterial translocation. This suggests a mechanism whereby jaundiced patients are susceptible to septic complication.     

Hyperbaric oxygen prevents bacterial translocation in rats with obstructive jaundice

This study was designed to demonstrate bacterial translocation following bile duct ligation and investigate preventive effects of hyperbaric oxygen on obstructive jaundice-related bacterial translocation in an animal model. Hyperbaric oxygen treatment significantly reduced the endogenous colony counts in distal ileum of normal rats both in the short (two days) and long (seven days) term. Endogenous bacteria in distal ileum significantly increased in bile duct ligated rats in the short and long term, and presence of bacterial translocation was proven by bacterial growth in mesenteric lymph nodes, liver, spleen, and blood. Short- and long-term hyperbaric oxygen treatments significantly reduced the intestinal colony counts and prevented the bacterial translocation almost completely in rats with bile duct ligation. It is concluded that obstructive jaundice causes bacterial overgrowth and translocation, and hyperbaric oxygen treatment can prevent both bacterial overgrowth and translocation effectively.     

Effects of glutamine and curcumin on bacterial translocation in jaundiced rats

AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used. METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, GroupⅠ received oral normal saline, Group Ⅱ received oral glutamine and Group Ⅲ received oral curcumin for seven day...     

Pathophysiology of increased intestinal permeability in obstructive jaundice

Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.     

Intestinal failure in obstructive jaundice

TO THE EDITOR We read with great interest the article by Ding LA and LiJS, which aimed to review the current knowledge on the physiology of normal intestinal barrier function and highlight the role of intestinal failure after various injurious insults in the development of septic complications or multiple organ failure with subsequent rapid clinical deterioration or even death.     

Somatostatin: possible cause of bacterial translocation in obstructive jaundiced rats

The purpose of this study was to examine the effect of endogenous somatostatin hormone on bacterial translocation in obstructive jaundiced rats. Five groups of rats were studied: group I (n = 10), non-operated group (control); group II (n = 10), sham-operated group which underwent laparotomy and dissection of portal elements, while the common bile duct was not ligated and somatostatin was not injected; group III (n = 10), same as group II, plus injection of somatostatin; group IV (n = 10), common bile duct was ligated with laparotomy but somatostatin was not injected; group V (n = 10), same as group IV, plus somatostatin injection. The blood was analyzed for somatostatin, alkaline phosphatase, and bilirubin levels on the third and tenth days in all animals. At study termination (tenth day), peritoneal swab and blood cultures were taken, and liver, spleen, lung, and mesenteric lymph nodes were harvested for microbiological studies. Bacterial translocation levels were higher in groups III, IV, and V when compared with levels in groups I and II. Similar translocation levels were obtained when blood somatostatin levels were comparable. However, the highest translocation rate was found in groups IV and V in which the blood somatostatin level was also higher when compared with that in other groups. This finding shows that blood somatostatin level is increased in obstructive jaundice. This may explain the bacterial translocation and related sepsis found in obstructive jaundice.     

梗阻性黄疸对肠黏膜屏障的影响

肠黏膜屏障包括机械屏障、免疫屏障、生物屏障和化学屏障,四者共同维持肠黏膜的正常防御功能。梗阻性黄疸患者引起肠黏膜屏障损伤,导致细菌移位及内毒素血症,后者又加重屏障功能障碍。本文主要就梗阻性黄疸对肠黏膜屏障损伤的机制作一综述。     

Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats

AIM: To observe the protective effect of glucagon-like peptide-2(GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase(ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14 th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A(Ig A) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group.RESULTS: In the rat model, jaundice was obvious, and the rats’ activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced Ig A expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group(P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group(P < 0.01).CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal Ig A and reduced bilirubin and endotoxin.     

Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

AIM： To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerati-ve colitis model. METHODS： Rats were randomly assigned to three groups： groupⅠ： control, group Ⅱ： experimental colitis, group Ⅲ： colitis plus melatonin treatment. On d 11 after colitis, plasma tumor necrosis factor-α, portal blood endotoxin levels, colon tissue myeloperoxidase and caspase-3 activity were measured. Bacterial translocation was quantified by blood, lymph node, liver and spleen culture. RESULTS： We observed a significantly reduced inciden-ce of bacterial translocation to the liver, spleen, mesen-teric lymph nodes, portal and systemic blood in animals treated with melatonin. Treatment with melatonin signifi-cantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid-trea-ted rats （16.11 ± 2.46 vs 32.97 ± 3.91, P 〈 0.01）. CONCLUSION： Melatonin has a protective effect on ba-cterial translocation and apoptosis.     

多巴胺调控实验性梗阻性黄疸围手术期肾髓质水通道蛋白2表达

目的:探讨梗阻性黄疸围手术期应用小剂量多巴胺对肾髓质水通道蛋白2(aquaporin 2)蛋白表达影响.方法:♂wistar大鼠70只随机分为4组,分别为对照组(n=10)、梗阻性黄疸组(n=20)、多巴胺5μg组(n=20)和多巴胺10μg组(n=20).梗阻性黄疸组及多巴胺组大鼠全身麻醉后建立梗阻性黄疸动物模型;对照组大鼠行假手术.7d后全麻下解除胆管梗阻,对照组再次行假手术.多巴胺组于胆管再通手术之前于股静脉套管针穿刺泵入多巴胺,剂量分别为5μg/(kg·min)和10μg/(kg·min);而假手术组及梗阻性黄疸组大鼠泵入9g/L生理盐水,泵注持续2h,并将各组动物随机均分为立即取材组和24h后取材组.腔静脉血离心后收集血清冻存检测胆红素、肌酐和尿素氮;分离肾脏髓质冻存,免疫印迹法(Western blotting)法检测aquaporin 2的表达.结果:解除梗阻早期鼠血清胆红素水平下降.血尿素氮及肌酐未见明显改变.通过Western blotting对肾髓质aqp2表达测定发现,梗阻性黄疸组解除梗阻0h取材组aqp2表达较对照组明显下降(15 665±1181 vs 21 966±1544,P<0.01),而解除梗阻24h后aqp2表达出现明显上升(36 490±1822 vs 21 917±2661,P<0.01).多巴胺5μg组0与24h aqp2表达更接近CO组(16 010±646,22 715±575 vs 21 966±1544,21 917±2661);10μg组各时间点aqp2表达与梗黄组接近(13 581±1662,32 313±1453 vs 15 665±1181,36 490±1822),未见多巴胺有明显调节aqp2表达作用.结论:胆管梗阻损伤肾脏集合管上皮细胞结构并抑制水重吸收功能;低浓度多巴胺可调控集合管水通道蛋白2表达.     

急性胆道梗阻肠黏膜屏障破坏与氯离子通道-2的关系

目的:探讨急性胆道梗阻肠黏膜屏障破坏与肠上皮细胞氯离子通道-2(chloride channel-2,CLC-2)的关系.方法:建立急性胆道梗阻(阻塞性黄疸)大鼠动物模型,术后7d连续注射Lubiprostone(Lu组)、类高血糖素多肽-2(GLP-2组)、两者共同使用(Lu+GLP组),以假手术组(Sham组)和阻...     

胆汁酸对失代偿期肝硬化大鼠肠道细菌过度生长和细菌移位的影响

目的观察胆汁酸对失代偿期肝硬化大鼠肠道细菌过度生长和移位的影响,为其临床应用提供依据。方法将37只伴有腹水的肝硬化大鼠及30只健康大鼠随机分为三组,分别采用结合胆汁酸甘氨胆酸(CG)、非结合胆汁酸熊去氧胆酸(UDCA)[均为70mg/(kg·d)]和安慰剂治疗2周。测定胆汁分泌速度、回肠细菌总数、细菌移位率。结果安慰剂组肝硬化大鼠胆汁分泌速度显著低于健康大鼠(P<0.001);胆汁酸治疗后速度增至正常水平。肝硬化大鼠回肠细菌总量显著高于健康大鼠(P<0.001),予胆汁酸治疗后降至正常水平。予胆汁酸的肝硬化大鼠细菌移位发生率显著低于安慰剂治疗组(P<0.01),存活率显著高于安慰剂组。结论失代偿期肝硬化大鼠应用结合或非结合胆汁酸可增加胆汁分泌、抑制肠道细菌过度生长,减少细菌移位的发生率,提高存活率。     

肝硬化大鼠模型肠壁结构及细菌移位的研究

目的 研究肝硬化大鼠模型肠黏膜结构的改变及细菌移位.方法 采用皮下注射40%四氯化碳诱导大鼠肝硬化模型,比较肝硬化大鼠模型与正常对照组小肠组织结构及超微结构的变化;将肝、脾和肠系膜淋巴结组织匀浆进行细菌培养,了解肠道细菌移位情况;采用鲎实验检测血浆内毒素水平.结果 与正常对照组相比,肝硬化模型组小肠绒毛表面积显著下降(P<0.01),而肠隐窝深度无明显变化(P>0.05),肠黏膜上皮细胞微绒毛明显缩短、稀疏,上皮细胞间紧密连接结构模糊,细胞间隙增大;肝硬化模型组肝、脾、肠系膜淋巴结细菌移位发生率分别为16.67%、16.67%和41.67%,正常对照组未发现细菌生长;肝硬化模型组血浆内毒素水平明显高于正常对照组(P<0.01).结论 肝硬化大鼠模型肠黏膜上皮组织及超微结构发生改变,从而导致肠道细菌移位和血浆内毒素水平的升高.     

急慢性大鼠梗阻性黄疸模型的建立

目的:探讨急慢性SD大鼠梗阻性黄疸模型的建立,评价其模拟临床梗阻性黄疸的价值,提供一种新型的慢性梗阻性黄疸模型.方法:SD大鼠随机分成3组,每组每时段6只:急性梗阻性黄疸模型组(A组),慢性梗阻性黄疸模型组(B组),对照组(C组).造模后于第1、2、3、4、5周分别抽取大鼠静脉血检查肝功能,显微镜下刻度目镜检测大鼠胆总管直径,光学显微镜观察肝组织的病理改变,其中第4周行胆总管十二指肠吻合再通.结果:A组造模术后4wk内黄疸进行性加重(TB:749.38μmol/L±38.99μmol/Lvs84.86μmol/L±49.09μmol/L,P<0.05),胆总管直径扩张明显(1.50cm±0.30cmvs0.35cm±0.15cm,P<0.05),肝细胞变性、坏死明显,伴有增生.第4周行胆总管与十二指肠端侧吻合后黄疸消退明显(TB:153.93μmol/L±57.36μmol/Lvs749.38μmol/L±38.99μmol/L).B组造模术后黄疸呈现波动性,胆总管直径扩张(0.20cm±0.15cmvs0.30cm±0.10cm,P<0.05),肝细胞以变性为主,并有纤维组织增生.第4周行胆总管与十二指肠端...     

B超联合磁共振胰胆管成像对梗阻性黄疸的诊断价值

目的探讨B超与磁共振胰胆管成像检查在梗阻性黄疸诊断中的价值。方法对66例梗阻性黄疸患者进行超声和MRCP检查,并给予手术治疗。结果 B超联合MRCP诊断梗阻性黄疸的正确率为92.4%,其中对13例胰头癌的诊断正确率为100%,13例壶腹部癌的诊断正确率为84.6%,19例胆管癌的诊断正确率为84.2%;对15例胆管结石的诊断正确率为100%,6例良性胆道狭窄为100%。结论 B超联合MRCP检查对诊断梗阻性黄疸有很高的临床应用价值。     

一氧化氮和内毒素在梗阻性黄疸致病机制方面的作用

梗阻性黄疸（obstructive jaundice，OJ）是临床常见的症状。梗阻性黄疸患者术后并发症和死亡率较高，常死于感染和败血症，提示机体术前的免疫功能受到了抑制。梗阻性黄疸可使网状内皮系统功能降低，细菌清除能力减弱。肠道来源的细菌和内毒素逃脱肝脏枯否细胞的监视，进入血液循环。有研究发现梗阻性黄疸常并发肠源性内毒素血症，内毒素激活枯否细胞，产生大量炎性介质，如一氧化氮（NO）、肿瘤坏死因子α（TNFα）及氧自由基等。     

Decreased expression of intestinal chemokine TECK/CCL25 in experimental obstructive jaundice and its reversal following internal biliary drainage

BACKGROUND: Although bacterial translocation is a significant problem in patients with obstructive jaundice, how translocation is promoted in this situation is not clearly understood. We previously reported the recovery of gut mucosal T-lymphocyte numbers in jaundiced rats following internal biliary drainage. This suggests that bile in the intestinal lumen promotes T-lymphocyte redistribution into the gut mucosa. To test this hypothesis, we have examined the expression patterns of chemokines that play an important role in lymphocyte recruitment into the small intestine. METHODS: Four groups of rats receiving one of the following surgical procedures were studied: a sham operation (SHAM), common bile duct ligation (CBDL), CBDL followed by external drainage, or CBDL followed by internal drainage. Expression levels of intestinal mRNAs encoding TECK, MECK, and LARC chemokines were assessed using real-time polymerase chain reaction. Distribution of chemokine mRNA in the rat ileum was examined using in situ hybridization (ISH). RESULTS: Following surgery, the expression levels of TECK mRNA decreased significantly in the CBDL group compared with in the SHAM group. While TECK expression did not recover after external drainage, it recovered to a near-normal level after internal drainage. Expression levels of MECK and LARC mRNAs were similar among all groups. ISH confirmed strong expression of TECK mRNA in the epithelial cells of the small intestine. CONCLUSIONS: These results indicate that bile may contribute to high expression levels of TECK/CCL25 mRNA in the small intestine. Bile may also have a role in regulating the distribution of gut mucosal T lymphocytes by promoting TECK production from epithelial cells.     

Extra-hepatic hepatocellular carcinoma presenting as obstructive jaundice

Hepatocellular carcinoma is a neoplasm with a uniformly poor prognosis. Risk factors for its development include chronic hepatitis B or C infection, haemochromatosis and alpha-1-antitrypsin deficiency, but individuals with any type of chronic liver disease are predisposed. The incidence is significantly higher in Asia and Africa although it has been noted to be increasing in the United States. We present a patient with notable atypical clinical features for hepatocellular carcinoma. The patient had neither predisposing risk factors nor a primary liver lesion causing obstructive jaundice. After multiple tissue specimens were obtained, the final pathological diagnosis was established. Hepatocellular carcinoma generally requires a surgical cure, but patients who are icteric often portend poorer prognoses. For those at high risk, screening may be indicated to identify early curative treatment.     

Mechanism of pancreatic hypersecretion in dogs with obstructive jaundice

Summary Pancreatic exocrine function in experimental obstructive jaundice was examined using dogs. Outputs of pancreatic juice, bicarbonate and amylase were greater in dogs with obstructive jaundice than in control dogs. To further examine the hypersecretory mechanism in obstructive jaundice, we examined pancreatic exocrine secretion stimulated by secretin and pancreozymin in both the isolated perfused pancreas and pancreatic dispersed cell culture. The perfused pancreas stimulated with secretin and pancreozymin in dogs with obstructive jaundice showed higher secretion of volume, bicarbonate and amylase than in control dogs. Dispersed pancreatic cells of jaundiced dogs stimulated by secretin and pancreozymin released more bicarbonate and amylase into the media than dispersed cells of control dogs. These data suggest pancreatic hypersecretion in obstructive jaundice is not due to excessive serum levels of secretin and pancreozymin or impaired metabolism of these hormones.