肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎的影响

目的探讨肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎（SBP）的影响。方法 采用高压液相色谱-示差法，检测45例住院肝硬化腹水患者（34例白发性腹膜炎和11例肝硬化无菌性腹水）治疗前后口服糖分子探针乳果糖、甘露醇后尿液排泄率比值（LAC／MAN）情况，评估病人肠黏膜通透性水平；采用鲎试剂三肽显色基质偶氮法检测病人治疗前后血浆内毒素（LPS）水平，另11例健康志愿者作为对照组结果治疗前肝硬化SBP尿LAC／MAN、血浆内毒素水平均显著高于无菌性腹水（SA）组和健康对照组（P均〈0．001）Pearson相关性分析：肝硬化腹水患者尿LAC／MAN改变与血浆LPS水平呈正相关（r=0．187，P〈0．001）治疗1周后肝硬化SBP患者尿LAC／MAN及血浆LPS水平平行下降。结论肝硬化SBP患者存在肠黏膜通透性异常，且肠黏膜通透性改变与内毒素血症有关．     

重度慢性乙型肝炎患者肠黏膜通透性的变化及相关因素分析

目的探讨重度慢性乙型肝炎患者肠黏膜通透性的变化并分析其相关因素。方法检测30例正常人（正常组）和90例重度慢性乙型肝炎患者（肝病组）的尿乳果糖/甘露醇（L/M）,以此作为肠黏膜通透性指标;同时测定两组的血清二胺氧化酶（DAO）、内毒素（ET）、肿瘤坏死因子-α（TNF-α）、肝功能指标（ALT、AST、TBIL、PT、A）等,分析上述指标与L/M的相关性。结果与正常组相比,肝病组L/M明显升高（P〈0.05）。直线相关性分析显示,肝病组的DAO、ET、TNF-α、TBIL、PT与L/M呈正相关（r=0.551、0.819、0.835、0.601、0.761,P均〈0.01）,与A呈负相关（r=-0.453,P=0.012）。进一步的多元逐步回归分析显示,L/M与ET、TBIL、DAO水平显著相关（r=0.819、0.868、0.896,P〈0.01或〈0.05）。结论重度慢性乙型肝炎患者的肠黏膜通透性较正常人显著增高,存在早期肠道屏障功能损伤;肠黏膜通透性与内毒素血症、高胆红素血症及血清DAO密切相关。     

肝硬化患者肠黏膜通透性与Child—Pugh分级的相关性研究

目的探讨肝硬化患者肠黏膜通透性（IP）与Child—Pugh分级的相关性及肠道去污剂对肝硬化患者肠道屏障功能及肝功能状态的影响。方法按Child—Pugh分级标准将76例肝硬化患者分为A、B、C3组,并选择30例体检者作为对照组,采用高压液相色谱法检测各组患者尿液乳果糖／甘露醇排出比（L／M）;给予76例肝硬化患者选择性肠道去污剂,比较用药前后各组患者肝功能Child—Pugh分级和肠黏膜通透性。结果肝硬化患者尿乳果N／甘露醇排出比明显高于对照组（0．208±0．025vs0．057±0．019）,肝硬化患者按Child。Pugh分级各组尿乳果糖／甘露醇排出比也均明显高于对照组,差异有显著性（P〈0．01）;采用Spearman等级相关分析发现,肝功能Child—Pu巾评分与乳果糖／甘露醇排出比呈正相关（r=0．658,P〈0．05）;给予肠道去污药物2周后肝硬化Child-Pugh分级各组患者尿液乳果糖／甘露醇排出比与治疗前比较均明显下降（P〈0．05）,各组Child—Pugh评分均有改善。结论肝硬化患者的肠黏膜通透性与肝功能Child—Pugh评分呈正相关,即肠道通透性随肝功能下降而升高,肠黏膜通透性对于肝硬化患者的诊断和治疗有临床意义。     

重度慢性乙型病毒性肝炎患者肠黏膜通透性的变化及其机制

目的:研究重度慢性乙型病毒性肝炎患者肠黏膜通透性的变化并探讨其病理生理机制.方法:采用高效液相色谱蒸发光散射器(HPLC-ELSD)检测30例正常人和30例重度慢性乙型肝炎患者尿中乳果糖和甘露醇排泄率的变化,以尿乳果糖/甘露醇排泄率的比值(L/M)反映肠黏膜通透性的变化.结果:与正常人相比,重度慢性乙型肝炎患者尿乳果糖的排泄率增加(0.0860±0.0225 VS0.0650±0.0270,P=0.002),尿甘露醇的排泄率无明显变化,而尿乳果糖/甘露醇排泄率的比值(L/M)明显升高(0.0430±0.0198 VS .0316±0.0134,P=0.011).结论:重度慢性乙型肝炎患者肠黏膜通透性增高,导致内毒素经肠道途径大量入血,引起内毒素血症,在重度慢性乙型肝炎发生,发展过程中发挥重要的病理生理作用.     

选择性肠道去污染对肝硬化自发性细菌性腹膜炎肠黏膜通透性的影响

目的观察肝硬化自发性细菌性腹膜炎（SBP）肠黏膜通透性和形态结构的变化及选择性肠道去污染对其通透性的影响。方法按诊断标准,将28例肝硬化SBP患者随机分为治疗组（15例）和对照组（13例）,在肝硬化腹水常规治疗和全身应用抗生素抗感染的基础上,治疗组加用诺氟沙星口服选择性肠道去污染（SDD）。采用酶联免疫吸附法（ELISA）测定治疗前后二胺氧化酶（DAO）、D-乳酸（D-Lac）和内毒素（ET）的水平;HE常规染色观察肠黏膜形态结构的变化。结果 常规治疗可降低DAO、D-Lac和ET水平（P〈0.05）,加用SDD可进一步减轻肠黏膜损伤,降低肠黏膜通透性,防止细菌移位。结论 SDD对肝硬化SBP肠黏膜屏障具有保护作用。     

肝硬化对肠黏膜屏障的损害

肝硬化是一种多病因的慢性疾病。肝硬化造成患者肠黏膜屏障的损害,使肠道内毒素和细菌进入血液或腹腔,造成内毒素血症及自发性腹膜炎,进一步加重了患者的病情,引起恶性循环。此文就肝硬化对肠黏膜的损害及其机制作一综述。     

胃动素和血管活性肠肽在不同部位及性质胆石症患者改变的临床研究

目的观察不同部位及性质胆石症患者胃动素(motilin,MTL)和血管活性肠肽(vasoactive intestinal peptide,VIP)含量变化,并探讨肠屏障功能在胆石形成中的作用和意义。方法选取2011年3月-2013年3月就诊于三六三医院且需进行手术治疗的胆结石患者108例,健康对照者20例,按结石部位不同分为4组:健康对照组(A1组,n=20)、胆囊结石组(B1组,n=36)、胆管结石组(C1组,n=36)、胆囊结石合并胆管结石组(D1组,n=36);所有入选患者全部行手术治疗,收集胆石进行化学分析;根据结石不同性质分为健康对照组(A2组,n=20)、胆固醇结石组(B2组,n=40)、胆色素结石组(C2组,n=52)、混合性结石组(D2组,n=16)。分别采用放射免疫分析法测定各组血浆及回肠末端黏膜组织中MTL和VIP的含量。结果不同部位结石患者血浆及肠黏膜组织MTL和VIP的含量变化:B1、C1、D1组与A1组比较差异有统计学意义(P0.05),B1组与C1组比较,C1组与D1组比较,D1组与B1组比较,差异均无统计学意义(P0.05);不同性质结石患者血浆及肠黏膜组织MTL和VIP含量变化B2、C2、D2分别与A2组比较,差异有统计学意义(P0.05),C2组分别与B2、D2组比较差异有统计学意义(P0.05),B2组与D2组比较差异无统计学意义(P0.05)。结论胆色素结石患者存在血浆及肠黏膜组织MTL和VIP含量的改变,胆色素结石形成与肠屏障功能损伤一定的相关性,肠屏障功能损伤可能在促进胆色素结石的形成中发挥一定的作用。     

醒脑静注射液对重型颅脑损伤患者肠黏膜通透性及血浆二胺氧化酶的影响

目的探讨醒脑静注射液对重型颅脑损伤患者肠黏膜通透性及血浆二胺氧化酶的影响。方法在该院接受治疗的重型颅脑患者86例,随机分成对照组和观察组各43例。对照组患者入院后接受常规治疗,观察组患者在对照组治疗方式的基础上,应用醒脑静注射液静脉滴注治疗。采用格拉斯哥昏迷评分(GCS评分)评价重型颅脑损伤患者病情的改善情况,并测定治疗前后重型颅脑损伤患者血浆二胺氧化酶和乳果糖排泄率水平。结果观察组患者总有效率高于对照组(P<0.05)。治疗后,观察组GCS评分高于对照组(P<0.01)。治疗后5、10 d,观察组患者血浆二胺氧化酶和乳果糖排泄率低于对照组(P<0.01)。结论醒脑静注射液治疗重型颅脑损伤疗效显著,能够缓解患者的病情,改善患者的肠黏膜通透性,保护患者肠道黏膜屏障功能。     

腹腔感染大鼠肠黏膜通透性的改变与E-cadherin蛋白表达的关系

目的:观察腹腔感染大鼠肠屏障损伤后肠通透性的变化,及其与E-cadherin蛋白表达的相关性.方法:健康成年♂Wistar大鼠40只,随机分为空白对照组(仅行单纯剖腹手术)和腹腔感染组(采用盲肠结扎穿孔法制作腹腔感染模型),术后12、24、36、48h取材,每组8只,处死后,距回盲部10cm处取回肠进行常规病理检查,同时测定肠绒毛高度、肠上皮损伤指数及相应时间点血浆D-乳酸含量,应用Western blot方法测定肠黏膜E-cadherin蛋白的水平.结果:腹腔感染12h后肠屏障开始出现明显损伤性改变:肠绒毛高度明显降低,肠黏膜损伤评分增加,血浆D-乳酸含量明显增加(P<0.01);24h损伤达到高峰:肠绒毛高度最低,肠黏膜损伤评分最大,血浆D-乳酸含量明显增高(P<0.05);随后肠屏障逐渐恢复,但48h组损伤程度仍显著高于对照组(P<0.01).与对照组比较,腹腔感染组E-cadherin蛋白表达量降低(P<0.01);实验组各组相比较,24h组E-cadherin蛋白水平最低,36h和48h时E-cadherin蛋白表达量开始降升高,但仍较对照组低(P<0.01).相关性检验发现血浆D-乳酸水平与E-cadherin蛋白含量具有明显负相关(r=-0.605,P<0.01).结论:腹腔感染状态下,肠屏障严重受损,肠黏膜通透性的改变与E-cadherin蛋白水平具有显著的相关性.     

Misoprostol reduces indomethacin-induced changes in human small intestinal permeability

This study examined whether indomethacin-induced increases in small intestinal permeability in man are prevented by concomitant administration of a prostaglandin analog (misoprostol). Twelve male volunteers were tested as baseline, following misoprostol alone (200 g, at –16, –12, –8.5, –4, –1.5, and +4 hr); following indomethacin alone (75 mg, at –8; 50 mg, –1 hr); and following coadministration of misoprostol and indomethacin as specified above. A 100-ml test solution containing 3-O-methyl glucose (0.2 g), D-xylose (0.5 g),l-rhamnose (1.0 g), and [⁵¹Cr]EDTA (100 Ci) was ingested at 8 AM, and a 5-hr collection made for marker analysis to assess active and passive carrier-mediated transport and trans- and intercellular permeation, respectively. Indomethacin increased the permeation of [⁵¹Cr]EDTA selectively, and this increase was significantly reduced by the coadministration of misoprostol. These changes were mirrored by changes in [⁵¹ Cr]EDTA-L-rhamnose urine excretion ratios, which indicates that paracellular permeability was specifically altered. This study supports the suggestion that NSAIDs alter intestinal permeability by a mechanism involving reduced prostaglandin synthesis and indicates that coadministration of misoprostol with NSAIDs may reduce the frequency and severity of NSAID-induced small intestinal inflammation.     

Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability

In previous open studies, misoprostol and metronidazole reduced nonsteroidal anti-inflammatory drug-induced intestinal permeability changes and inflammation respectively. We assessed the effects of indomethacin treatment (50 mg three times a day) for one week with either coadministered metronidazole (400 mg twice a day, group 1,N=9) or misoprostol (200 g four times a day, group 2,N=7) on intestinal permeability to [⁵¹Cr]EDTA and mannitol in healthy volunteers, using double-blind, placebo-controlled, randomized techniques. Given alone, neither metronidazole nor misoprostol affected [⁵¹Cr]EDTA permeation, whereas indomethacin alone increased it from 1.20 (0.40) [mean percent urinary recovery (sd) groups 1 and 2] to 2.43 (0.72),P<0.002. Coadministered metronidazole (group 1) prevented this increase [1.10 (0.39) before, 1.55 (0.54) after,P>0.05], whereas misoprostol (group 2) did not [1.31 (0.51) before, 3.26 (1.10) after,P=0.005]. No drug regimen altered mannitol permeation. Indomethacin and misoprostol did not affect urinary recovery of intravenously administered probes. The results with metronidazole, if related to its antibacterial effects, support evidence from animal models that bacteria contribute to NSAID-induced intestinal damage. The previously reported reduction of indomethacin-induced increased permeability by misoprostol during a one-day study is not seen when the drugs are used in standard clinical doses for one week.Dr. Davies is partly supported by a grant from Searle and Dr. Wilkie by a grant from Bayer.     

Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study.

BACKGROUND: Cirrhosis is associated with intestinal barrier failure, related in part to enterocytes oxidative damage via xanthine oxidase overactivity. Experimentally, allopurinol, a xanthine oxidase inhibitor, reduces enterocytes' damage and bacterial translocation. AIM: To assess the short-term effects of allopurinol on intestinal permeability, oxidative stress and endotoxin-dependent cytokines in patients with cirrhosis. METHODS: Nineteen patients with cirrhosis, in a stable condition (age: 56 years; Child A/B/C: 6/7/6; ascites: 12; alcoholic cirrhosis: 16/19; abstinence >2 weeks), were included. At baseline and day 10 of allopurinol 400 mg/day, intestinal permeability [lactulose/mannitol (Lac/Man) ratio test], oxidative stress (serum malondialdehyde), as well as TNF-soluble receptor-1, IL-6 and lipopolysaccharide-binding protein (which reflects exposition to endotoxin) were measured. RESULTS: Malondialdehyde decreased significantly (-23%, P<0.05), whereas no effects were seen on intestinal permeability and the endotoxin-associated systemic inflammatory response. At baseline, portal pressure correlated to the Lac/Man ratio (r=0.55, P<0.02). At day 10, changes in malondialdehyde correlated to changes in the Lac/Man ratio (r=0.51, P<0.05). CONCLUSIONS: A 10-day course of allopurinol in patients with cirrhosis is associated with a significant reduction in oxidative stress but no effect on intestinal permeability and inflammatory markers. Whether intestinal damage in cirrhosis can be accessible to antioxidant therapy requires further study.     

Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission

Objective. Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004±0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008±0.006 (p=0.0005) in the same period. Conclusions. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.     

Bile acids reversible effects on small intestinal permeability

To define the action of deconjugated bile acids on the small intestinal permeability in an in vitrosystem, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a doserelated manner the trans epithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.     

Increased intestinal permeability as a predictor of bacterial infections in patients with decompensated liver cirrhosis and hemorrhage

Background and Aim: There have been no trials comparing the prophylactic effect of oral quinolone and intravenous cephalosporin antibiotics and elucidating the predictive factors for the occurrence of bacterial infections in cirrhotic patients with gastrointestinal bleeding in Asian‐Pacific region. Methods: One hundred and thirteen patients with advanced liver cirrhosis and active gastrointestinal hemorrhage were enrolled in our study. The patients were randomly allocated into either the oral ciprofloxacin group (n = 50, 500 mg every 12 h) or the intravenous ceftriaxone group (n = 63, 2.0 g per day for 7 days). Results: Proven or possible infections were significantly more frequent in the patients in the oral ciprofloxacin group (34.0%) than the intravenous ceftriaxone group (14.3%, P = 0.002). The intestinal permeability index (IPI, mean [SD]) measured the day after admission was significantly higher in the patients with proven or possible infections (1.45 [0.96]) compared with the no infection group (0.46 [0.48], P < 0.01). By multivariate analysis, oral ciprofloxacin prophylaxis and higher IPI at the time of inclusion were independent and significant predictors for proven or possible infections. By receiver operating characteristic curve analysis, the best cutoff value of IPI for the prediction of the occurrence of bacterial infection was 0.62%. Conclusions: The frequency of proven or possible infections was significantly lower in the intravenous ceftriaxone group compared with the oral ciprofloxacin group. The IPI measured the day after admission is a good clinical parameter predicting the occurrence of infection in these patients.     

Effects of experimental hemosiderosis on intestinal morphology,permeability, and tissue iron content

Effects of iron overload on intestinal function and structure are unknown and were, therefore, investigated. Sprague-Dawley rats were randomized into an iron-overloaded group, which received a single subcutaneous injection of 1,2 g/kg elemental iron-dextran complex, and placebo-treated pair-fed controls. Animals were studied after a 10-month observation period. Intestinal permeability was assessed by measuring the urinary excretion of lactulose, rhamnose, and mannitol after oral administration. In addition, tissue nonheme iron content was measured, and histologic examination and morphometric measurements were carried out. The chronic iron-overloaded group showed a significant increase in intestine tissue iron content and stainable iron in the submucosa and muscularis propria and adipose tissue of the small intestine and lamina propria and muscularis mucosa of the large intestine. There was a significant decrease in the crypt depths without discernible change in the intestine permeability to any of the markers used. In addition, the iron-overloaded animals showed a significant number of iron-laden cells, which primarily consisted of macrophages, fibroblasts, myocytes, and adipocytes. In contrast, no iron-laden cells were present in tissues obtained from the normal control group. Thus, chronic experimental iron overload in rats leads to significant morphologic, but no permeability, alterations of the alimentary tract.