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     

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。     

大鼠急性坏死性胰腺炎肠黏膜屏障功能障碍的观察

目的: 观察急性坏死性胰腺炎(ANP)大鼠肠黏膜屏障功能的变化。方法: SD大鼠80只随机分为假手术组(n=40)和ANP组(n=40)。胆胰管内逆行注射5%牛磺胆酸钠溶液制作ANP模型。观察大鼠胰腺和回肠的病理变化,动态测定肠脂肪酸结合蛋白(IFABP)、内毒素水平及肠系膜淋巴结和门静脉血细菌移位率。结果: 模型制作后2h血清IFABP明显升高,6h达到峰值(P<0.01),24h后降低。早期内毒素水平有明显升高,48h达到峰值(P<0.01)。肠系膜淋巴结细菌移位在ANP24h后明显升高,48h达到6/8只(P=0.013),门静脉血细菌移位48h达到3/8只(P=0.216)。结论: ANP早期肠黏膜屏障功能受损,引发肠道细菌和内毒素移位,IFABP可能是ANP早期肠黏膜屏障功能受损的预警指标。     

18例非失血性休克患者输血后临床分析

目的：研究休克患者输血后出现的病情变化与再灌注综合征的关系。方法：回顾性总结分析１９９３年１月～１９９７年１月我院收治的１８例非失血性休克患者输血前后临床表现比较。结果：１８例患者均发生病情突然恶化,其中６６７％（１２／１８）发生在输血４～２４ｈ内,１３例死亡,５例恢复正常。结论：休克患者输血后病情恶化可能与缺血 再灌注损伤有关。提出对非失血性休克患者输血应持慎重态度,若必须输血,则应在休克早期进行,同时注意预防再灌注损伤。     

PAF拮抗剂BN50739对大鼠急性肺损伤的作用研究

目的 观察PAF拮抗剂BN50739在治疗烧伤内毒素血症所致的急性肺损伤中的作用，为临床治疗提供依据。方法 采用烧伤复合内毒素血症大鼠模型，于致伤前5min腹腔注射BN50739。动态观察肺病理改变、血气分析、支气管肺泡灌洗液（BALF）中蛋白含量及肺内TNF表达。结果 BN50739可以明显减轻肺水肿，使BALF中蛋白含量明显低于生理盐水对照组，使伤后1.5h和6h血氧分压明显提高。BN50739尚能部分抑制TNF表达。结论 BN50739能部分改善烧伤复合内毒素血症所致的急性肺损伤。     

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。     

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.     

Effects of severe acute pancreatitis on gut bacteria/endotoxin translocation in pigs

Objective： To set up a swine model of severe acute pancreatitis（SAP） and to observe its relationship with the gut-originated bacteria/endotoxin translocation. Methods： Forty pigs weighing 17-22 kg were randomly diyided into SAP group （n=34） and sham-SAP group （n=6）. By injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8 000-10 000 benzoyl arginine ethyl ester（BAEE） units trypsin per milliliter into pancreas via pancreatic duct, SAP was induced under anesthesia. Endotoxin samples from vena cava were determined by chromogenic limulus amebocyte lysate （LAL） technique. Both portal and central vena blood samples were collected before and 72 h after the induction of SAP and cultured for both aerobic and anaerobic bacterial growth. Animals were sacrificed at the end of experiments by injecting 20 ml of 10% KCl intravenously and tissue specimens of mesenteriolum and mesocolon lymph nodes, lung, pulmonary portal lymph nods and pancreas were taken immediately after animal death, and homogenized for bacteriological studies. Results： Systemic plasma endotoxin levels increased rapidly 6 h post induction of SAP（PIS） with a peak at 48 h PIS （P〈0.01）. The magnitude of bacterial translocation in both portal and systemic blood and remote systemic organs as well were recovered PIS. Conclusion： （1） A swine model of SAP was established; （2）The early endotoxemia PIS seamed probable originated from gut endotoxin translocation; （3）The magnitude of bacterial translocation in both portal and systemic blood and the remote systemic organs as well were recovered at 72h PIS.     

氧自由基损伤在烫伤大鼠延迟复苏后肠道细菌和内毒素移位中的作用

为了了解烧伤延迟复苏后肠粘膜氧自由基损伤情况及其对肠源性细菌、内毒素移位的影响，将６６只悉生大鼠分为以下四组：（１）对照组（ｎ＝６）。（２）立即复苏组（ｎ＝２４），４０％烫伤后立即按Ｐａｒｋｌａｎｄ公式复苏。（３）延迟复苏组（ｎ＝２４），伤后６小时开始复苏。（４）药物治疗组（ｎ＝１２），大鼠延迟复苏加上维生素Ｃ、Ｅ联合治疗。在伤后８、２４、４８和７２小时活杀动物（各时间点６只）进行下列指标检测：回肠粘膜超氧化物歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨＰｘ）及丙二醛（ＭＤＡ）含量，回肠粘膜病理形态学观察、二胺氧化酶（ＤＡＯ）活性，血和肠系膜淋巴结、肝、脾、肾、肺细菌培养，血浆内毒素水平。结果显示，伤后ＳＯＤ、ＧＳＨＰｘ含量下降，ＭＤＡ升高，同时肠粘膜病理改变加重、ＤＡＯ活性下降，血和脏器细菌移位率、血浆内毒素水平增高。这些改变在延迟组更明显，使用维生素Ｃ、Ｅ治疗后减轻。表明，烧伤延迟复苏加重肠粘膜氧自由基的损伤，促进肠道细菌和内毒素移位。     

Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats

Background  Chemotherapy causes breakdown of the intestinal barrier, which may lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side effects; however, its effect on the intestinal barrier is unknown. Previous studies show that granulocyte colony-stimulating factor (G-CSF) plays an important role in modulating intestinal barrier function, but these studies are not conclusive. Here, we investigated the effects of paclitaxel on the intestinal barrier, and whether G-CSF could prevent paclitaxel-induced bacterial translocation.

Methods  Twenty-four male Sprague-Dawley rats were divided into three groups: control group, paclitaxel group and paclitaxel + G-CSF group. Intestinal permeability was measured by the urinary excretion rates of lactulose and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver were aseptically harvested for bacterial culture. Endotoxin levels and white blood cell (WBC) counts were measured and bacterial quantification performed using relative real-time PCR. Jejunum samples were also obtained for histological observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling staining. One-way analysis of variance and Fisher’s exact test were used to compare differences between groups.

Results  Paclitaxel induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by G-CSF treatment. Apoptosis in the control group was 0.6%. Paclitaxel treatment also resulted in villus atrophy, increased intestinal permeability and a reduction in the WBC count. G-CSF treatment resulted in increased villus height and returned WBC counts to normal levels. No bacterial translocation was detected in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were culture-positive in the liver, spleen and mesenteric lymph nodes, respectively. Bacterial translocation was partially inhibited by G-CSF.

Conclusions  Paclitaxel disrupts the intestinal barrier, resulting in bacterial translocation. G-CSF treatment protects the intestinal barrier, prevents bacterial translocation, and attenuates paclitaxel-induced intestinal side-effects.

     

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 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.     

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.     

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。     

乳果糖对门脉高压大鼠肠粘膜屏障功能保护作用的研究

目的探讨乳果糖对肝硬化门脉高压大鼠肠粘膜屏障功能的保护作用。方法50只雄性SD大鼠皮下注射50%CCl4橄榄油溶液,制造门脉高压模型。造模后存活大鼠随机分为：（1）治疗组;（2）对照组;（3）模型组。治疗组即乳果糖组,灌服乳果糖5mL/kg,每日2次,直至大鼠排稀便（共10d）;对照组仅灌服葡萄糖水。11d后处死取全血及肝、脾、肾、和肠系膜淋巴结组织匀浆后作细菌培养,测细菌易位率;采用改良的偶氮基质显色法行内毒素测定;取回肠粘膜组织行HE、Masson染色和超微病理的观察研究;采用免疫组织化学方法测定回肠末端紧密连接蛋白（occludin）表达水平。结果治疗组细菌易位发生率较对照组和模型组均明显降低（P〈0.05）;与模型组、对照组比较,治疗组肝功能显著改善（P〈0.01）;治疗组血清内毒素水平（0.20±0.08）Eu/mL亦明显低于对照组、模型组之（0.33±0.06）Eu/mL、（0.44±0.07）Eu/mL（P〈0.01）;紧密连接蛋白的表达,治疗组与对照组、模型组比较,亦具有显著性差异（P〈0.01）。结论口服乳果糖可以改善肠道屏障功能,减少门脉高压大鼠肠道菌群易位,减轻内毒素血症,从而一定程度上改善肝功能。     

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。     

胆道梗阻患者肠道细菌易位的临床观察

对３５例胆道疾病患者的肠系膜淋巴结、外周静脉血、门静脉血及胆汁进行细菌学研究。３５例中胆道梗阻２３例，胆道未梗阻１２例。结果显示：６５％的胆道梗阻患者出现细菌易位，而非胆道梗阻患者未见细菌易位发生；易位至肠系膜淋巴结者多为Ｇ－肠杆菌。提示肝外胆道梗阻可导致人体肠道细菌易位。     

胰十二指肠切除术后肠黏膜屏障损伤及SIRS与肠道细菌移位的关系

目的探讨胰十二指肠切除术后肠黏膜屏障损伤与肠道细菌移位的关系。方法将50例行胰十二指肠切除术患者术前及术后24、48、72 h检验全血细菌DNA、血浆D-乳酸和内毒素水平与空白对照组比较。结果术前所有患者细菌DNA PCR结果均为阴性,术后72 h内PCR检测阳性10例(20.00%),术后SIRS组与无SIRS组差异有统计学意义(P<0.01)。空白对照组与病例组术前血浆D-乳酸和内毒素水平差异无统计学意义(P>0.05),病例组术后各时段血浆D-乳酸和内毒素均显著高于术前(P<0.05),胰十二指肠切除术后患者血浆D-乳酸和内毒素呈正相关(P<0.05)。PCR阳性组血浆D-乳酸和内毒素显著高于PCR阴性组(P<0.01),SIRS组血浆D-乳酸和内毒素显著高于无SIRS组(P<0.01)。结论胰十二指肠切除术后肠黏膜屏障损伤、SIRS与肠道细菌移位密切相关,细菌DNA PCR有助于早期诊断肠道细菌移位。     

胆道梗阻患者肠道细菌易位的临床观察

对３５例胆道疾病患者的肠系膜淋巴结,外周静脉血,门静脉血及胆汁进行细菌学研究。３５例中胆道梗阻２３例,胆道未梗阻１２例。结果显示：６５％的胆道梗阻患者出现细菌易位,而非胆道梗阻患者未见细菌易位发生,易位至肠系膜淋巴结者为Ｇ＾－肠杆菌,提示肝外胆道梗阻可导致人体肠道细菌易位。     

L-arginine在高原鼠肝脏缺血再灌注损伤时肠道细菌易位中的作用研究

目的:探讨肝脏缺血再灌注损伤时肠道细菌易位的机制及精氨酸能否有效改善肠道细菌易位。方法:在大鼠肝脏缺血再灌注损伤模型基础上,对门静脉血、回肠系膜淋巴结进行肠道细菌培养。结果:肝脏缺血再灌注损伤时,血液及淋巴结可能培养出大肠埃希氏菌。但精氨酸预处理组与相同阻断时间组之间无差异。结论:高原地区第一肝门阻断的时间对肠道细菌易位有显著影响,但精氨酸对肝缺血再灌注损伤的肠道细菌易位无明显的保护作用。