急性重症胰腺炎肠粘膜屏障功能改变的临床研究

目的:探讨急性重症胰腺炎(SAP)时肠粘膜屏障功能改变机制.方法:20例SAP入院当天采血检测二胺氧化酶(DAO)、内毒素(endotoxin,ET)、肿瘤坏死因子(TNFα)、一氧化氮(NO)的浓度.并用带特殊电化学检测器的高压液相色谱法(HPLC)检测尿中乳果糖与甘露醇排泄率比值.以10名健康志愿者作为正常对照组.结果:同正常对照组相比较,SAP患者尿中乳果糖与甘露醇排泄率比值明显升高(P＜0.01);血中ET、NO、TNFα、DAO的水平显著增加(P＜0.01).结论:在急性重症胰腺炎患者中,肠粘膜屏障受损,肠粘膜通透性增高.ET、NO、TNFα单独或协同参与肠粘膜屏障的损害.DAO可反映肠道粘膜的完整性.     

活血化瘀中药对清解通下中药增效作用的实验研究Ⅱ--对急性细菌性腹膜炎大鼠肠粘膜通透性的影响

目的:研究活血清下汤对急性细菌性腹膜炎大鼠肠粘膜通透性的影响.方法:采用盲肠结扎加穿孔法制作腹膜炎动物模型,将大鼠随机分为正常对照组、模型对照组、抗生素组、复方丹参方组、加味小承气汤组和活血清下汤组,每组6只动物,术后72 h以乳果糖(L)、甘露醇(M)混合溶液灌胃,高效液相色谱法测定二者在尿中的含量和比值,以反映肠粘膜通透性的大小.结果:细菌性腹膜炎大鼠尿中乳果糖/甘露醇比值显著高于正常组(P＜0.01),主要由于尿中乳果糖含量较高引起;各治疗组乳果糖/甘露醇比值均有所降低,尤以活血清下汤组效果显著(P＜0.05或0.01).结论:急性细菌性腹膜炎可引起肠粘膜通透性增高,活血清下汤有保护肠粘膜屏障功能的作用,使肠粘膜通透性增高受到抑制.     

抑制急性坏死性胰腺炎细菌移位的实验研究

目的观察不同方法对急性坏死性胰腺炎(ANP)并发感染的防治效果.方法将86只大鼠随机分为4组对照组(n＝20)、ANP组(n＝22)、乳果糖组(n＝22)及导泻加抗生素组(n＝22).于光镜下观察肠粘膜损伤情况,并用镧作示踪剂观察肠粘膜通透性和肠粘膜细胞的渗透性;另切取胰腺组织、肠系膜淋巴结和抽取腹水作细菌培养.结果ANP组、乳果糖组和导泻加抗生素组细菌移位与对照组比较差异有统计学意义(P＜0.05),且前3组组间细菌移位差异亦有统计学意义(P＜0.05),乳果糖组和导泻加抗生素组能明显改善肠道屏障的病理变化,在光镜下ANP组、乳果糖组及导泻加抗生素组之间肠粘膜损伤程度比较差异有统计学意义(P＜0.01).结论乳果糖和导泻加抗菌治疗能减少细菌移位,保护肠粘膜,是防治ANP并发感染的有效措施.     

气相色谱用于肠通透性监测的研究

作者采用国产气相色谱及９２０２微机数据处理系统，对临床患者和实验动物肠通透性改变进行监测。该方法以甘露醇（Ｍ）和乳果糖（Ｌ）为探针，用气相色谱检测尿中糖分泌率及Ｌ／Ｍ比值。结果显示，测定标准品Ｍ和Ｌ随进样量增加而呈线性改变，与国外学者报道一致。比较不同浓度进口与国产乳果糖，证明二者在研究肠通透性方面高度相关（ｒ＝０．９９）。检测急性胰腺炎并发感染动物的尿标本，发现乳果糖大量排出，Ｌ／Ｍ值明显增加。作者认为，气相色谱为一行之有效的方法用于肠通透性监测，有助于临床上对内源性感染及脓毒症的早期诊断。     

两种糖分子探针用于测定重症胰腺炎时肠通透性的改变

目的:观察甘露醇和乳果糖用于测定重症胰腺炎时肠通透性的改变.方法:杂种犬15条,随机分为对照组和实验性急性坏死性胰腺炎(ANP)组.发病后给犬灌服甘露醇和乳果糖混合液,收集6小时尿,气相色谱法测定其含量,并作脏器细菌培养.结果:胰腺炎组尿中乳果糖/甘露醇(L/M)比值高出对照组2～12倍,于发病后第2天最为显著.所有动物都出现了肠道细菌移位,血培养阳性率为100%,以发病后48小时内最高.对照组只有2条犬在肠系膜淋巴结培养出细菌.血培养全部阴性.结论:ANP发病后48小时内肠粘膜屏障即遭到严重破坏,发生肠道细菌移位,成为胰腺感染的来源.     

术后禁食患者肠通透性的变化

目的　测定术后病人肠通透性 ,评价其肠屏障功能。方法　 2 0例中等大小手术的病人 ,术后禁食 3～ 5 d,肠功能恢复时 ,口服乳果糖 (L )和甘露醇 (M)溶液 ,收集 6 h尿液 ,用高压液相色谱议测定尿中 L和 M,计算其排泄比率 (L / M)。选 2 0例健康志愿者为对照 ,两组的年龄、性别无统计学差异。结果　术后禁食病人的 L / M为 0 .1989± 0 .1186 ,健康志愿者为 0 .4398± 0 .2 16 5 ,两者有显著性差异 (P <0 .0 5 )。结论　与健康志愿者比较 ,术后禁食病人的肠通透性升高     

大鼠失血性休克肠粘膜形态学与功能变化

目的 探讨失血性休克肠缺血/再灌注损伤后,粘膜屏障功能与形态学的变化。方法 制作大鼠失血性休克模型,以休克复苏后0h、1h、3h、6h、12h、24h时间段取回肠组织标本,通过光镜和电镜下进行肠粘膜的形态学改变的观察,包括组织学检查、肠粘膜及绒毛厚度测量、粘膜损伤指数评定;同时在肝门静脉血作内毒素测定及复苏后1h、3h、6h的尿液作乳果糖/甘露醇比值检测以分析肠粘膜屏障功能的改变。结果 肠粘膜损伤主要表现出凋亡、坏死的两种细胞死亡形式。复苏0h组粘膜上皮就发生明显损伤改变,1h进一步加重,3h组出现修复现象,6h部分空肠及回肠绒毛已修复,12h时大部分肠粘膜结构基本恢复正常;内毒素和乳果糖/甘露醇比值在6h组达到高峰,仅24h组才恢复正常。结论 失血性休克缺血-再灌注后,肠粘膜屏障早期受累,表现为回肠粘膜细胞凋亡及坏死的两种损伤形式;肠粘膜具有强大的修复潜能;肠屏障功能的恢复滞后于形态学修复。     

胃肠癌患者肠黏膜通透性与营养状态、免疫功能及炎症反应的关系

目的 探讨胃肠癌患者肠粘膜通透性的改变是否与其营养状态、免疫功能及炎症反应的变化有关.方法 124 例胃肠癌患者按营养危险指数(NRI)分为正常营养(NN)组、临界或轻度营养不良(BMM)组和重度营养不良(SM)组.检测各组的营养、免疫、炎症指标及乳果糖/甘露醇比值(L/M),观察肠粘膜通透性与其营养状态、免疫功能、炎症反应之间的相互关系.结果 SM 组和BMM 组PAB、ALB、TF 均较NN 组低;BMM 组的营养、免疫指标低于NN 组(P&lt;0.01),L/M 在SM组和BMM 组与其自身的ALB、TF、IgG、IgA、CD3、CD4、CD4/CD8 直线负相关,与PAB、TLC 直线负相关(P&lt;0.05),与CD8、CRP 直线正相关(P&lt;0.01).结论 胃肠癌合并严重营养不良患者肠粘膜屏障损害较胃肠癌合并临界或轻度营养不良患者严重,其肠粘膜屏障损害程度与自身的营养状态、免疫功能呈负相关,与炎症反应呈正相关.     

清热解毒方剂对腹腔感染大鼠肠黏膜屏障功能的影响

目的:观察腹腔感染状态下大鼠肠黏膜形态学和通透性的变化,观察肠源性内毒素体内移位途径,探讨清热解毒方剂肠屏障保护作用的机制.方法:采用人工胃液联合大肠杆菌腹腔内注射的方法建立大鼠腹腔感染模型.将Wistar大鼠分为3组:正常对照组(C组)、模型组(M组)、清热解毒方剂组(QRJD组),分别观察造模后6 h,24 h,72 h回肠的病理学改变以及尿液中乳果糖与甘露醇的比值(L/M)的变化.采用荧光化学发光法检测门静脉、乳糜管淋巴液、腹主动脉血以及肠系膜淋巴结、肝、肺、肠、脾组织FITC-LPS荧光强度.结果:模型组肠黏膜损伤,尿液L/M显著升高,脏器组织中FITC-LPS含量由高至低为:肠系膜淋巴结、肺、肝、肠、脾,体液中FITC-LPS含量以乳糜管淋巴液含量最高.清热解毒方剂组上述指标较模型组明显改善.结论:清热解毒方剂可以显著减轻大鼠腹腔感染所致肠黏膜损伤,改善肠黏膜通透性,减少肠源性内毒素移位,改善肠道屏障功能.     

Effect of Intervention Therapy Based on Liver-spleen Correlation Theory on Intestinal Mucosal Barrier Function in Patients with Chronic Severe Hepatitis

[目的]观察应用肝脾相关理论干预慢性重型肝炎的临床疗效及探讨其对肠黏膜屏障的保护作用.[方法]选取慢性重型肝炎患者60例,采用简单随机法将患者随机分为对照组(基础治疗+凉血解毒法)30例和观察组(基础治疗+凉血解毒法+健脾益气法)30例,疗程2周,共2个疗程,观察治疗前后症状积分、血清学变化和治疗后总有效率,同时观察2组患者的肠黏膜通透性(血清二胺氧化酶水平、尿中乳果糖/甘露醇排出率)和血浆内毒素水平.[结果]观察组的总有效率(80.0％)优于对照组(66.7％),差异有显著性意义(P＜0.05).2组均可改善临床症状,改善肝功能,升高凝血酶原活动度,且观察组作用优于对照组,差异有显著性意义(P＜0.05);2组治疗前内毒素水平、尿中乳果糖/甘露醇排出率比较,差异均无显著性意义(P＞0.05),治疗后观察组血浆内毒素水平、尿中乳果糖/甘露醇排出率较治疗前显著降低(P＜0.05),且与对照组比较差异有显著性意义(P＜0.05).[结论]应用肝脾相关理论治疗慢性重型肝炎可提高临床疗效,并可改善慢性重型肝炎患者肠黏膜屏障功能,纠正肠源性内毒素血症.     

Increased intestinal permeability associated with infection in burn patients

Thermal injury may be associated with disruption of normal gut barrier integrity. To test this hypothesis, we assessed intestinal permeability with the nonmetabolizable, poorly absorbed disaccharide lactulose, which is efficiently excluded by the normal intestinal mucosa. Permeability studies were performed in 15 burned patients (aged 18 to 67 years; mean burn size, 40%) and 11 healthy controls. Lactulose, 10 g, was administered enterally, together with 5 g of mannitol as a control, and urinary excretion rates were determined. Lactulose excretion and the lactulose/mannitol excretion ratio increased threefold (160 +/- 30 vs 57 +/- 7 mumol and 0.113 +/- 0.033 vs 0.035 +/- 0.005) in the infected patients (sepsis score, 10 +/- 2; burn size, 38% +/- 6%). In contrast, noninfected burn patients (sepsis score, 0) had permeability values similar to those of controls (66 +/- 10 mumol and 0.036 +/- 0.007). Permeability increased as the severity of infection increased. Infection in burn patients is associated with increased bowel permeability. The intestine may be a primary source of sepsis. Alternatively, the systemic response to infection may alter gut barrier function, which could facilitate translocation of bacteria and absorption of endotoxin.     

Changes in Intestinal Permeability after Roux-en-Y Gastric Bypass

Background

Roux-en-Y gastric bypass (RYGB) interferes considerably with the anatomy and physiology of the gastrointestinal tract. The study of intestinal permeability can provide important information regarding changes in the structure and function of the mucosal barrier after the procedure.

Methods

The urinary excretion rates of lactulose and mannitol after oral intake of both substances were evaluated. We also evaluated the lactulose/mannitol excretion ratio. Tests were performed during the preoperative period (T0), at the first postoperative month (T1), and at the sixth postoperative month (T6).

Results

The study included 16 morbidly obese patients. The excretion rate of mannitol was significantly lower at T1 compared with T0 and T6 (p?=?0.003). There was no significant difference in the excretion rates of lactulose or in the lactulose/mannitol ratio during the three periods. Six patients (37.5 %) exhibited a considerable increase in the excretion rate of lactulose at T6 (4–73 times higher than the preoperative value), accompanied by proportional variations in the lactulose/mannitol ratio.

Conclusions

The significant increase in mannitol excretion rate from T1 to T6 most likely reflects the occurrence of intestinal adaptation (mucosal hyperplasia), which would tend to minimize the malabsorption of macronutrients. A subgroup of patients who undergo RYGB exhibit pronounced increase in their intestinal permeability (assessed by the lactulose/mannitol ratio and the lactulose excretion rate) at T6.     

A single dose of endotoxin increases intestinal permeability in healthy humans

To investigate the effects of endotoxin on gut barrier function, we performed paired studies of intestinal permeability in healthy humans (N = 12) receiving intravenous Escherichia coli endotoxin (4 ng/kg) or 0.9% saline solution. Two nonmetabolizable sugars, lactulose and mannitol, which are standard permeability markers, were administered orally, 30 minutes before and 120 minutes after the test injection. The 12-hour urinary excretion of these substances after endotoxin/saline solution administration was used to quantitate intestinal permeability. After endotoxin administration systemic absorption and excretion of lactulose increased almost two-fold (mean +/- SEM, 263 +/- 36 mumol per 12 hours vs 145 +/- 19 mumol per 12 hours during saline studies). Similar but less marked alterations in mannitol absorption and excretion occurred after endotoxin injection (5.7 +/- 0.3 mmol per 12 hours vs 4.9 +/- 0.3 mmol per 12 hours). When individual 12-hour lactulose excretion after endotoxin administration was related to the magnitude of systemic responses, a significant relationship occurred between lactulose excretion and elaboration of norepinephrine and between lactulose excretion and minimum white blood cell count. These data suggest that a brief exposure to circulating endotoxin increases the permeability of the normal gut. These observations are consistent with the hypothesis that during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.     

Intestinal permeability is increased in burn patients shortly after injury

There is increasing direct experimental and indirect clinical evidence to indicate that under certain conditions intestinal barrier function may be lost in trauma victims. No direct measurements, however, have been performed in patients to determine whether intestinal permeability is increased shortly after a major thermal injury in the absence of infection. Fifteen hemodynamically stable burn patients with burns on more than 20% of their body surface (39% +/- 12%) had their intestinal permeability measured within 24 hours of injury with use of the two nonmetabolizable sugars lactulose and mannitol as permeability markers. Lactulose absorption was fourfold higher in the patients (223 +/- 54 mumol) than in the controls (58 +/- 11 mumole; p less than 0.02), whereas the lactulose/mannitol ratio was threefold higher (5.2 vs 1.7; p less than 0.05). Thus intestinal permeability was increased in patients with moderate to major burn injuries shortly after injury.     

Alterations in intestinal permeability after thermal injury.

Alterations in intestinal permeability have been postulated to occur after thermal injury. We evaluated the status of intestinal permeability during the first 2 postburn weeks in 15 subjects by measuring the differential excretion of enterally administered lactulose and mannitol. The mean age and burn size of the patients were 32.7 +/- 3.6 years and 53.3% +/- 5.1% of the total body surface area, respectively. Ten healthy volunteers were also studied. The lactulose-mannitol excretion ratio was 0.159 +/- 0.017 for the patients and 0.017 +/- 0.003 for controls. The increased ratio did not correlate with burn size or postburn day. Patients who developed significant clinical infections during their first 2 postburn weeks had lactulose-mannitol ratios on postburn day 2 that were significantly higher than those of controls and patients who did not develop infections. This suggests a relationship between susceptibility to infection and early alterations in intestinal permeability.     

Effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients

The aim of the study was to analyse the effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients. A total of 22 patients with severe burns were randomly divided into an early enteral feeding group (EF) and a delayed enteral feeding group (DF). The levels of serum endotoxin and TNF-alpha were dynamically detected in the members of both groups, and two unmetabolized sugars (lactulose and mannitol) were orally administered to these patients 1, 3 and 5 days postburn. Intestinal permeability was evaluated by detecting the concentrations of lactulose and mannitol in the urine and the lactulose-mannitol ratio (L/M) ratio. The levels of serum endotoxin and TNF-alpha in severely burned patients were significantly higher than in normal subjects (P<0.01). The endotoxin level was positively related to the TNF-alpha level (rEF=0.93, P<0.01; rDF=0.80, P<0.05). The urinary lactulose levels in both groups were significantly higher than in normal (P<0.01), the urinary mannitol levels showed no obvious changes (P>0.05). The urinary L/M ratios in both groups were significantly higher than in normal subjects (P<0.01). The urinary L/M ratio was positively related to the serum endotoxin level (r=0.95, P<0.01). The urinary lactulose levels and the urinary L/M ratios in the EF group were significantly lower than in the DF group (P<0.01). The levels of serum endotoxin and TNF-alpha in the EF group were significantly lower than in the DF group (P<0.01). It is suggested that intestinal permeability was markedly higher after burns than normal, and was positively related to the gut-derived endotoxemia. Early enteral feeding may decrease intestinal permeability, preserve the intestinal mucosal barrier and have a beneficial effect on the reduction of enterogenic infection.     

Evaluation of intestinal mucosal permeability function in patients with acute pancreatitis

This study aims to evaluate the intestinal mucosal permeability in patients with acute pancreatitis. The lactulose:mannitol (L:M) ratio was used to assess permeability. It is an inexpensive and quite reliable method. The intestinal permeability was increased in patients with acute pancreatitis compared with the controls. In addition, patients with severe pancreatitis had higher intestinal barrier dysfunction compared with patients with mild pancreatitis, the L:M ratio being .2 and .029, respectively. It was also concluded that the permeability increased gradually over the course of pancreatitis and was maximum at day 7 (P < .01). This provides a window of opportunity for therapeutic intervention to prevent the late observed increase in intestinal permeability.     

肝细胞生长因子对移植小肠通透性及细菌易位的作用

目的探讨肝细胞生长因子（hepatocyte growth factor,HGF）对移植小肠通透性及细菌易位的作用。方法以Wistar大鼠20只为受体,SD大鼠20只为供体行异位全小肠移植,并以环孢素A（6mg/kg.d）肌注抑制排斥反应。HGF组（n=10）用微量输液泵持续均匀输入HGF（150μg/kg.d）,对照组（n=10）输入等量生理盐水,随机选取同批正常Wistar大鼠作为正常基准（n=10）。第7天两组实验动物均分别以乳果糖/甘露醇液2ml（含乳果糖100mg、甘露醇50mg）行移植小肠灌注,采集24h尿液检测乳果糖、甘露醇含量及乳果糖/甘露醇比值;第8天采集移植小肠肠系膜淋巴结及门静脉血行细菌培养,小肠组织学观察。结果对照组尿液中乳果糖含量为0.0931%±0.0085%,乳果糖/甘露醇比值为0.132±0.021,与正常基准0.0150%±0.0020%和0.020±0.005比较,差异均有统计学意义（P〈0.05）;HGF组乳果糖含量为0.0396%±0.0090%,乳果糖/甘露醇比值为0.056±0.013,与正常基准比较差异均有统计学意义（P〈0.05）,且低于对照组（P〈0.05）。HGF组移植小肠肠系膜淋巴结细菌阳性率为10%,对照组为60%,差异有统计学意义（P〈0.05）。HGF组门静脉血细菌阳性率为10%,对照组为20%,差异无统计学意义（P〉0.05）。两组移植小肠组织学观察仅见少量炎性细胞浸润。结论HGF能够降低同种移植小肠的通透性及细菌易位率,改善小肠黏膜屏障功能。     

手术创伤应激下肠黏膜通透性的改变及肠内肠外营养作用的比较

目的研究手术创伤对肠黏膜通透性的影响,并研究肠内和肠外营养对肠黏膜通透性的不同作用.方法 40例腹部手术的患者随机分为肠内营养(EN)组和肠外营养(PN)组,分别于术后3～11d予等氮、等热卡营养支持,并分别于术前1 d、术后7 d和术后12 d,测定口服含乳果糖10 g、甘露醇5 g的测试液后6 h尿中乳果糖和甘露醇排泄率的比值(L/M)变化,用高压液相色谱法测定尿中乳果糖和甘露醇的浓度.结果术前、术后7 d和术后12 d L/M比值EN组分别为0.026±0.01 7、0 059±0.026、0 027±0 017;PN组分别为0 025±0 013、0 080±0.032、0 047±0.021.术后7 d两组L/M比值较术前均显著升高,且PN组明显高于EN组;术后12 d L/M比值PN组仍明显高于术前及EN组,而EN组与术前无明显差异.结论创伤应激早期肠黏膜通透会有明显升高,在创伤的早期需注意维护肠黏膜屏障功能;肠内营养有较好的维护肠黏膜屏障功能的作用.