Effects of lactulose on intestinal endotoxin and bacterial translocation

Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats.
Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51Cr in the intestine.
Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by lactulose.
Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.     

梗阻性黄疸与肠粘膜屏障功能的实验研究

目的 了解梗阻性黄疸时小肠粘膜的病理改变。方法 无菌条件下结扎大鼠总胆管,取末端回肠观察其组织学改变,测量小肠粘膜的绒毛高度,绒毛面积和肠粘膜厚度;计算内脏细菌移位率。结果 在光镜下观察到总胆管结扎组肠粘膜萎缩,绒毛水肿,部分上皮细胞脱落;绒毛平均高度、绒毛平均面积和粘膜平均厚度减少。在电镜下观察到微绒毛稀疏,排列紊乱,内质网数目少且结构不完整;线粒体数目少,轻度肿胀,膜不清楚,嵴少而乱,内有空泡     

Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats.Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node ( MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary ^99mTc-diethylenetriamine pentaacetatic acid (^99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of ^51Cr in the intestine.Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO,which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose.Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.     

Effects of platelet activating factor antagonist (BN50739) on gut mucosal injury in acute severe pancreatitis in pigs

Objective To study the role of platelet activating factor (PAF) in the pathogenesis of intestinal mucosal injury and endotoxin/bacterial translocation in acute severe pancreatitis (ASP) in pigs.
Methods ASP was induced by intraductal injection of a mixture of sodium taurocholate and trypsin. BN50739, a specific antagonist of PAF, was given 30 min prior to the induction of ASP. Mucosal blood flow, mucosal myeloperoxidase (MPO) and malondialdehyde (MDA) were determined. Intestinal injury was observed microscopically. Portal blood endotoxin levels and the bacterial counts in the portal blood, intestinal lymph nodes and the pancreas were determined.
Results Prior antagonism of PAF by BN50739 reduced intestinal injury, increased intestinal mucosal blood flow, and reduced blood levels of endotoxin and bacterial counts in the portal blood, mesenteric lymph nodes and pancreas.
Conclusions Intestinal mucosal injury developed in ASP. PAF is responsible for the injury. Antagonism of PAF by BN50739 can improve intestinal microcirculation and reduce the severity of intestinal mucosal injury, which may decrease endotoxin/bacterial translocation.     

乌司他丁对手术创伤后肠屏障功能的影响

肠道是外科应激反应的中心器官之一。当外科应激反应过度或失调时，肠黏膜屏障的完整性首先遭到破坏，原先寄生于肠道内的微生物及其毒素经过通透性增高的肠黏膜进入血液循环，触发全身炎性反应(SIRS)和多器官系统衰竭(MOSF)，反过来又可加重肠黏膜坏死和细菌移位，形成恶性循环。腹部重大手术具有典型的外科应激反应。术后由于细胞因子和炎性介质等作用，可出现肠黏膜水肿、通透性增高，肠绒毛高度降低，肠系膜血管收缩，血流量减少，从而损伤肠黏膜的屏障功能。乌司他丁可能通过抗手术应激、减轻SIRS、改善免疫功能等作用，保护肠黏膜屏障功能。作者就乌司他丁对手术创伤应激后肠黏膜屏障功能的影响作一综述。     

益生菌对炎症性肠病小鼠肠道菌群紊乱及细菌移位的影响

目的探讨植物乳杆菌（LP）对炎症性肠病（IBD）小鼠肠道菌群及细菌移位的影响。方法采用白介素10基因敲除（IL-10^-/-）小鼠作为IBD动物模型,将8周龄雌性小鼠随机分成空白对照组、IL-10^-/-组和IL—10^-/- ＋LP组三组。IL-10^-/- ＋LP组每日灌胃0．5mLLP菌液（1．0×10^9 CFU／mL）,其余两组灌胃Ringer缓冲液0．5mL,持续4周。以小鼠粪便中的双歧杆菌、乳酸杆菌、肠杆菌和产气荚膜梭菌数量及肠系膜淋巴结、脾脏细菌移位为检测指标。结果IL-10^-/-小鼠肠内双歧杆菌、乳酸杆菌含量明显下降,肠球菌、产气荚膜梭菌含量升高,且肠道细菌移位明显增加;而连续灌胃LP菌液4周后,益生菌发挥了对肠道的调节作用,纠正了肠道菌群失衡,并降低了肠道细菌移位。结论LP能纠正炎症性肠病小鼠肠道菌群紊乱,减少细菌移位,从而增强了肠道屏障功能。     

益生菌对炎症性肠病小鼠肠道菌群紊乱及细菌移位的影响

目的 探讨植物乳杆菌(LP)对炎症性肠病(IBD)小鼠肠道菌群及细菌移位的影响.方法 采用白介素10基因敲除(IL-10~(-/-))小鼠作为IBD动物模型,将8周龄雌性小鼠随机分成空白对照组、IL-10~(-/-)组和IL-10~(-/-)+LP组三组.IL-10~(-/-)+LP组每日灌胃0.5 mL LP菌液(1.0×10~9CFU/mL),其余两组灌胃Ringer缓冲液0.5 mL,持续4周.以小鼠粪便中的双歧杆菌、乳酸杆菌、肠杆菌和产气荚膜梭菌数量及肠系膜淋巴结、脾脏细菌移位为检测指标.结果 IL-10~(-/-)小鼠肠内双歧杆菌、乳酸杆菌含量明显下降,肠球菌、产气荚膜梭菌含量升高,且肠道细菌移位明显增加;而连续灌胃LP菌液4周后,益生菌发挥了对肠道的调节作用,纠正了肠道菌群失衡,并降低了肠道细菌移位.结论 LP能纠正炎症性肠病小鼠肠道菌群紊乱,减少细菌移位,从而增强了肠道屏障功能.     

乌司他丁对梗阻性黄疸肠粘膜屏障功能影响的实验研究

目的 探讨梗阻性黄疸对肠粘膜屏障功能的影响及乌司他丁(UTI)的保护作用.方法 取雄性SD大鼠72只,随机均分为假手术组(A组)、梗阻性黄疸组(B组)、UTI干预组(C组),每组又分术后3、5、7、10 d4个时相.采用胆总管结扎法建立梗阻性黄疸模型.C组从术后第1天始每天腹腔注射UTI 40 000IU/kg,A组和B组用等量生理盐水作对照.检测各时相肝功能,血浆内毒素,取肠系膜淋巴结、肝、脾组织行细菌培养,光镜观察末端回肠粘膜形态改变,并用病理图像分析系统测量肠绒毛高度及粘膜厚度.结果 各时相肝功能指标、血浆内毒素B组较A组升高(P＜0.01);C组较B组降低(P＜0.01);血浆内毒素C组较A组术后3 d时相差异无统计学意义(P＞0.05).细菌移位率B组较A组升高(P＜0.01);C组较B组降低(P＜0.05);C组与A组相比,差异无统计学意义(P＞0.05).B组术后第3天即见肠粘膜受损改变,随时间推移进行性加重;C组较B组肠粘膜损害明显减轻.B组各时相小肠绒毛高度、粘膜厚度均低于A组(P＜0.01);C组则较B组升高(P＜0.01或P＜0.05);C组较A组术后3 d时相差异无统计学意义(P＞0.05).结论 梗阻性黄疸早期即可导致肠粘膜屏障功能受损,且随时间延长进行性加重;UTI对梗阻性黄疸时受损的肠粘膜屏障功能具有保护作用,对早期病变效果更好.     

急性胰腺炎肠黏膜损伤情况及通透性改变的实验研究

目的：观察实验性重症急性胰腺炎（ANP）鼠肠通透性的改变,并观察肠黏膜形态变化及细菌移位的关系。方法：实验性大鼠41只,随机分为胰腺炎组和对照组。利用电子显微镜以硝酸镧作为踪剂观察肠黏膜通透性和肠细胞的渗透性。结果：回肠黏膜出现明显病理改变,肠黏膜通透性和肠细胞渗透性明显增高。胰腺炎组肠系膜淋巴结和腹水标本培养出肠道菌属者,结论：ANP时存在着严重的肠道屏障功能损伤。发病时肠黏膜即遭到严重破坏,肠通透性增高,从而引起肠道细菌移位。     

谷氨酰胺对化疗大鼠肠黏膜屏障功能影响的实验研究

目的：探讨谷氨酰胺对5-氟尿嘧啶化疗大鼠肠黏膜屏障功能的影响。方法：实验分成4组：空白对照组（A组）;5-氟尿嘧啶化疗组（B组）;5-氟尿嘧啶＋甘氨酸组（C组）;5-氟尿嘧啶＋谷氨酰胺组（D组）;比较给药后各组外周血内毒素水平,肠系膜淋巴结及肝脏细菌移位率,空肠及结肠湿重、绒毛高度、绒毛宽度、黏膜厚度等指标。结果：血内毒素水平,肠系膜淋巴结及肝脏细菌移位率B组、C组比A组、D组明显增高,有统计学差异（P〈0.05）;空肠及结肠湿重、绒毛高度、绒毛宽度、黏膜厚度B组、C组、D组较A组降低,有统计学差异（P〈0.05）。结论：谷氨酰胺对5-氟尿嘧啶化疗大鼠的肠黏膜屏障功能具有保护作用。     

雌激素对创伤失血性休克肠道细菌移位的影响

目的探讨雌激素对创伤失血性休克(Trauma/hemorrhageshock,T/HS)肠粘膜屏障损伤以及肠道细菌移位的影响。方法雌性青春期Wistar大鼠40只,随机分为卵巢切除组10只,对照组10只,雌二醇组10只,大剂量雌二醇组10只,观察T/HS60min,复苏4h后的肠粘膜损伤程度(Chiu氏评分),并取肠系膜淋巴结、肝组织及门静脉血进行细菌培养,改良鲎试剂法测定血浆内毒素含量。结果雌二醇组和大剂量雌二醇组与其他两组相比,肠粘膜Chiu氏评分显著降低,细菌培养计数及内毒素含量明显减少,P均<0.05。结论雌激素能改善创伤失血性休克大鼠的肠粘膜损伤程度,降低肠道细菌及内毒素移位的发生率。     

早期肠内营养对急性胰腺炎的肠源性细菌移位及免疫应答功能的影响

目的 :探讨早期肠内营养在减缓急性胰腺炎细菌及内毒素移位以及改善宿主免疫应答功能中的作用。方法 :将 80只SD大鼠分 4组 ,6 0只用胆胰管注射法制成急性胰腺炎模型 ,其中 30只行肠造瘘进行肠内营养 ,30只行肠外营养 ;余 2 0只分别不形成急性胰腺炎模型 ,各用 1 0只行肠内外营养 ;检测的血内毒素水平 ,外周血、脾、肠系膜淋巴结CD4、CD8淋巴细胞亚群 ,并进行肠系膜淋巴结细菌培养。结果 :与AP/TPN组相比 ,AP/EN组回肠绒毛高度比AP/TPN组明显高 ,P <0 .0 5 ;内毒素水平AP/TPN组为 (0 .4 89± 0 .1 6 2 )EU·ml-1 ,比AP/EN组的 (0 .1 1 2± 0 .0 0 8)EU·ml-1 明显高 ,P <0 .0 5 ;AP/TPN及AP/EU中细菌种属无差别 ,均为肠内细菌 ,但与AP/TPN组相比AP/EN组细菌量显著减少 ;肠系膜淋巴结、脾及外血中CD4 /CD8比率AP/EN组比AP/TPN组明显高 ,P <0 .0 5 ,差异有显著性。结论 :AP中早期肠内营养能很好耐受 ,EN可维持正常肠结构从而减少细菌及内毒素移位 ,并可维持宿主的免疫应答功能。     

血小板激活因子拮抗剂对急性重症胰腺炎肠粘膜损伤的影响

目的 :观察血小板激活因子拮抗剂对急性重症胰腺炎 (SAP)时肠粘膜损伤以及细菌和内毒素移位的影响。　方法 :采用胰管内注射牛磺胆酸钠 胰蛋白酶的方法诱导猪SAP ,对照组用等渗盐水代替牛磺胆酸钠 胰蛋白酶进行胰管内注射。为了解血小板激活因子 (PAF)的特异性拮抗剂BN5 0 739对SAP肠粘膜损伤的影响 ,在诱导SAP之前 30min静脉注射BN5 0 739。测定肠粘膜血流量、肠粘膜内髓过氧化酶 (MPO)和丙二醛 (MDA)含量 ,观察肠粘膜的病理改变 ,并测定门静脉血的内毒素含量和门静脉血、肠系膜淋巴结、胰腺的细菌数量。　结果 :诱导SAP以前给予BN5 0 739能够增加肠粘膜血流量 ,减少肠粘膜MPO和MDA含量 ,降低门静脉血的内毒素浓度和移位细菌数量。　结论 :SAP时合并有肠粘膜损伤 ,用BN5 0 739拮抗PAF能够增加肠粘膜血流量、改善肠粘膜微循环、减轻肠粘膜的炎性细胞浸润和降低MDA和MPO含量 ,减轻肠粘膜损伤的严重程度 ,减少内毒素和细菌移位的数量     

一氧化氮对内毒素血症大鼠肠道损伤及细菌移位的影响

目的 一氧化氮（NO）参与休克的血管扩张,血压下降,但它对组织损伤,特别是肠道的损伤及细菌移位的作用仍不十分清楚。本实验以NO合酶（NOS）底物左旋精氨酸及其抑制剂硝基左旋精氨酸（LNNA）为工具,观察NO对内毒素血症时大鼠肠道损伤及细菌移位的影响。方法 用内毒素（LPS,10mg/kg,ip）复制内毒素血症模型,给予LNNA或L-arg抑制或促进NO合成,测定肠道质过氧化物丙二醛（MDA)的含量,二胺氧化酶（DAD）活性及肠系膜淋巴结细菌培养。结果 LPS可降低肠细胞DAO活性,增加MDA含量和肠系膜淋巴细菌移位的发生率和细菌数量;用LNNA抑制NO后可加重LPS的上述作用,而给予L－arg促进NO合成则可减轻LPS的作用。结论 本实验结果表明在内毒素血症时,抑制NO可加重肠道损伤和细菌移位的发生,提示NO对肠组织有一定的保护作用。     

赤芍加清胰汤联合早期空肠营养对大鼠重症急性胰腺炎肠屏障功能的保护作用

目的观察赤芍加清胰汤联合早期空肠营养对大鼠重症急性胰腺炎肠屏障功能的保护作用。方法采用胰胆管内逆行注射5%牛黄胆酸钠复制重症胰腺炎大鼠模型。32只重症胰腺炎大鼠随机分为模型对照组(A组)、清胰汤加赤芍治疗组(B组)、早期空肠营养组(C组)、清胰汤加赤芍联合早期空肠营养组(D组),每组8只。B组在手术清醒后及术后8h中药汤剂灌胃;C组术后12h予肠内营养;D组在B组治疗基础上,于术后12h加用肠内营养,A组在D组给药相同时间点分别给予等量的生理盐水灌胃及经营养管注入空肠。术后24h处死动物。处死前1h将一段长约20 cm小肠两端夹闭,向其内注入FITC-dextran溶液1ml以观察肠黏膜通透性;无菌采取肠系膜淋巴结及门静脉血检测其中的细菌量;取门静脉血测定血浆D-乳酸及内毒素水平。结果 (1)肠黏膜通透性:4组血浆D-乳酸及FITC-dextran水平比较,A组>B组、C组>D组,差异均有统计学意义(P<0.05),B组、C组间差异无统计学意义(P>0.05)。(2)细菌移位情况:细菌培养及内毒素水平检测结果显示,A组>B组>C组>D组,差异均有统计学意义(P<0.05)。结论赤芍、清胰汤、空肠营养三者联合治疗,能明显降低重症急性胰腺炎大鼠肠黏膜通透性,起到保护肠屏障功能的作用。     

EPIDERMAL GROWTH FACTOR PREVENTS INCREASED PERMEABILITY AND BACTERIALTRANSLOCATION IN RATS WITH ACUTE PANCREATITIS

INTRODUCTION Acute pancreatitis may induce an increase in mucosal permeability and subsequent translocation of enteric bacteria and their endotoxins (1,2). The fact that most bacteria associated with acute pancreatic and peripancreatic infections are of enteric origin implies that the gut plays a major role in the pathogenesis of pancreatic infection (3). Epidermal growth factor (EGF), which plays a key regulatory role in controlling gut mucosal proliferation and turnover, is required fo…     

清热通下中药对胆管炎大鼠肠屏障保护和炎症反应调控的研究

目的:探讨清热通下中药在急性胆管炎治疗中对肠黏膜屏障保护和炎症调控的作用.方法:60只SD大鼠分为3组,每组20只.模型组(A组)制作急性胆管炎模型;治疗组(B组)制作急性胆管炎模型并喂清热通下中药治疗;假手术组(C组)仅剖腹后缝合.取血检测细胞因子、炎症介质、内毒素和细菌移位等指标.结果:A组白细胞介素-6(interleukin-6, IL-6)、白细胞介素-8(interleukin-8, IL-8)、肿瘤坏死因子α(tumor necrosis factor-α, TNF-α)、血清C反应蛋白(C reactive protein, CRP)和一氧化氮(nitric oxide, NO)明显高于B组和C组(P<0.01),IL-2则显著低于B组和C组(P<0.01);A组的血清内毒素和肝、脾、肠系膜淋巴结细菌移位数显著高于B组和C组(P<0.01).结论:具有清热通下作用的中药在治疗急性胆道感染中具有保护肠黏膜屏障、降低血清内毒素和调节机体炎症反应的作用.     

庆大霉素对截瘫大鼠肠道细菌移位影响的实验研究

目的探讨庆大霉素灌胃和肌注两种不同给药方式对脊髓损伤并发截瘫大鼠肠道细菌移位的影响。方法建立大鼠脊髓损伤性截瘫模型,以庆大霉素灌胃治疗和肌注治疗两组大鼠为实验组,以脊髓损伤生理盐水灌胃和肌注两组大鼠为相应对照组。采集动物下腔静脉血进行内毒素定量检测和细菌培养,采集肝、脾、肠系膜淋巴结、肠内容物作细菌培养并进行菌种鉴定。取实验组和对照组各动物的肝、脾、肠系膜淋巴结、空肠、回肠进行病理切片及染色检查。结果庆大霉素灌胃组内毒素低于其他三组,血细菌培养仅生理盐水灌胃组阳性率高,脾细菌培养仅生理盐水肌注组阳性率高;肠系膜淋巴结细菌培养、庆大霉素灌胃组阳性率低,而生理盐水灌胃组阳性率高。结论本研究提示在预防及治疗脊髓损伤性截瘫后并发细菌／内毒素时应以经胃肠道途径给药为主。     

Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs

Background One of the major causes of death in severe acute pancreatitis （SAP） is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition （EIN） as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs. Methods SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition （PN） or elemental enteral nutrition （EEN） or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes （MLN）, liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum. Results Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury （ileum mocosa thickness, villus height, and crypt depth） were significantly alleviated by EIN （P〈0.05）. Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group. Conclusion Our results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more effective treatment for SAP dogs.     

酪酪肽对急性胰腺炎细菌易位的影响

目的:探讨酪酪肽(PYY)对急性胰腺炎大鼠肠粘膜的屏障功能。方法:SD大鼠40只,雌雄不拘,采用经腹腔注射精氨酸建立急性胰腺炎大鼠模型后,随机分为对照组(n=20)及治疗组(n=20),治疗组给与PYY皮下注射,治疗后第48h处死大鼠,测定肠粘膜组织匀浆丙二醛(MDA)含量、肠粘膜蛋白含量以及肠管细菌易位率。结果:治疗组动物肠粘膜蛋白含量显著高于对照组(P<0.01);肠粘膜组织匀浆MDA含量显著低于对照组(P<0.01);肝脏及脾脏细菌培养阳性率显著低于对照组(P<0.05)。结论:PYY对急性胰腺炎大鼠肠黏膜屏障具有保护作用。