大鼠急性胰腺炎肠道细菌易位的实验研究

目的 本实验是观察大鼠急性胰腺炎后经胃肠道给予庆大霉素或各氨酰胺对肠道细菌易位的影响。方法 结扎封闭群Wistar大鼠的胆管，制成急性胰腺炎模型。分假手术组、急性胰腺炎组、庆大霉素组和各氨酰胺组4组。各组又分5个亚组，分别于术后24、48、72、96和144小时处死动物。无菌下取回盲部淋巴结、胰腺、脾、肝、门静脉血和盲肠内容做细菌培养、计数。胰腺和小肠组织做病理检查。结果 表明大鼠急性胰腺炎发生后，肠系膜淋巴结细菌数和阳性率明显增高，与门静脉血比较有显差异。庆大霉素组盲肠内容和肠系膜淋巴结的大脑杆菌数明显减少，革兰氏阳性菌明显增多。谷氨酰胺组盲肠内容和肠系膜淋巴结的细菌数均显减少。结论 大鼠急性胰腺炎发生后早期肠道细菌易位主要经肠系膜淋巴途径。经胃肠道给予谷氨酰胺可防止肠道内细菌易位，减少胰腺感染的发生。     

急性坏死性胰腺炎肠道细菌移位的实验研究

采用大鼠制戚急性胰腺炎(AP)动物模型后24或72h取盲肠及胰腺组织、肠系膜淋巴结、胆汁、血液作细菌学检查．通过对照组进行比较分析．证实了AP时肠道细菌可移位至胰腺，病变越重，细菌移位率越高，肠系胰淋巴结、胆道是肠道细菌发生移位的重要途径。     

参附注射液对实验性急性坏死性胰腺炎肠道细菌移位的影响

目的：研究参附注射液对实验性急性坏死性胰腺炎（ANP）时肠道细菌移位的影响。方法：ANP大鼠制模方法采用胰腺被膜下注射牛磺胆酸钠。假手术组、对照组经皮下注射生理盐水，实验组同法给予等量参附注射液。取标本（下腔静脉血、腹水、肠系膜淋巴结及大肠内容物）进行细菌培养，计数菌落数及鉴定细菌种类。结果：标本中生长的细菌与大肠内容物培养细菌种类相同，实验组标本的菌落数少于对照组（P〈0.01）。结论：实验性ANP大鼠合并感染的细菌来源于肠道，参附注射液可以减少肠道细菌移位。     

中药三七总苷对急性坏死性胰腺炎大鼠肠道细菌易位的影响

目的 探讨中药三七总苷对急性坏死性胰腺炎(ANP)大鼠的治疗作用及肠道细菌易位的影响。方法 逆行胆胰管注射5％牛磺胆酸钠溶液制成ANP模型。90只大鼠随机分为假手术组、ANP组和治疗组，每组各30只。每组10只观察1周生存率；另每组各20只观察术后不同时相血清淀粉酶及胰腺、肝、脾、肺和肠系膜淋巴结细菌培养情况及病理组织学变化。结果 治疗组的存活率明显高于ANP组．术后12h及24h血清淀粉酶明显低于ANP组，治疗组胰腺、肝、脾、肺及肠系膜淋巴结细菌培养阳性率亦低于ANP组．治疗组病理损害明显轻于ANP组。结论 中药三七总苷可保护肠黏膜屏障从而减少肠道细菌易位。     

庆大霉素肠管去污染对大鼠实验性胰腺炎时细菌易位的影响

目的探讨庆大霉素对实验鼠肠管去污染预防重症胰腺炎并发胰腺感染性坏死的效果。方法经胰胆管插管注射无菌的５％牛磺胆酸钠制成大鼠重症胰腺炎模型。大鼠分成重症胰腺炎组（１组）;轻型胰腺炎组（２组）;重症胰腺炎加盲肠给予庆大霉素组（３组）;重症胰腺炎加庆大霉素肌肉注射组（４组）和实验对照组。术后观察各组大鼠回肠系膜淋巴结、胰腺、肝脏和血液的肠源性细菌培养阳性率。结果实验后７２小时,１组大鼠（１１只）肠系膜淋巴结培养阳性率为１００％（１１／１１）,胰腺和肝脏分别为８２％（９／１１）和２７％（３／１１）,但血液培养阴性。２组（１０只）大鼠肠系膜淋巴结培养阳性仅３０％（３／１０）,余器官培养结果均为阳性;３组（１２只）肠淋巴结和胰腺组织培养阳性率分别为４２％（５／１２）和３４％（４／１２）;而４组大鼠肠淋巴结、胰腺、肝脏和血液培养阳性率依次为１００％（１１／１１）、９１％（１０／１１）、９％（１／１１）、９％（１／１１）。结论经肠管直接给予庆大霉素去污可降低重症胰腺炎感染并发症,经肌肉注射则否。     

实验性梗阻性黄疸肠道细菌易位及精氨酸治疗的研究

目的观察梗阻性黄疸（梗黄）大鼠肠道细菌易位状况及经胃肠道给予精氨酸对肠道细菌易位的影响。方法结扎Wistar大鼠胆管，制成梗黄模型，60只Wistar大鼠随机分为假手术组、梗黄组和梗黄＋精氨酸治疗组，每组各20只，于术后21d观察并比较各组血浆内毒素、肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）的含量及肝功能状况，并对肠系膜淋巴结、胰腺及肺组织行细菌培养，末端小肠做病理检查。结果梗黄组大鼠血浆内毒素、TNF-α、IL-6含量、总胆红素及谷丙转氨酶均明显升高，肠系膜淋巴结、胰及肺组织细菌培养阳性率明显升高，小肠黏膜损伤严重，而精氨酸治疗组以上血清学指标较梗黄组均显著下降，肠系膜淋巴结、胰及肺组织细菌培养阳性率明显降低，小肠黏膜病理损害程度明显减轻。结论梗黄后出现的高内毒素血症与肠道细菌易位关系密切。精氨酸治疗可减轻梗黄时肠道细菌易位，从而降低血浆内毒素水平及细胞因子的过表达。     

大鼠急性出血坏死性胰腺炎时细菌移位和茵陈蒿合承气汤的影响

目的 :研究大鼠急性出血坏死性胰腺炎 (牛磺胆酸钠胰胆管注射诱导 )细菌移位及其机制和茵陈蒿合承气汤的影响。 方法 :大鼠分成模型组、中药防治组、假手术组。术后观查外周血、门静脉血内毒素水平 ;肝、脾、胰、肠系膜淋巴结细菌移位率 ;盲肠内容物需氧菌总量和革兰阴性杆菌菌量 ;肠推进功能。 结果 :急性出血坏死性胰腺炎时外周血和门静脉血内毒素水平显著升高 ;肝、胰、肠系膜淋巴结组织细菌移位率显著升高 ;盲肠需氧菌总量和革兰阴性杆菌量显著升高 ;肠推进功能降低。应用茵陈蒿合承气汤能显著改善上述指标。 结论 :急性出血坏死性胰腺炎时存在细菌移位 ,茵陈蒿合承气汤能有效地减少急性出血坏死性胰腺炎时细菌移位的发生     

大鼠急性出血坏死性胰腺炎细菌移位和茵陈蒿合承气汤的影响

目的：研究大鼠急性出血坏死性胰腺炎（牛磺胆酸钠胰胆管注射诱导）细菌移位及其机制和茵陈蒿合承气汤的影响。方法：大鼠分成模型组、中药防治组、假手术组。术后观察外周血、门静肪血内毒素水平;肝、脾、胰、肠系膜淋巴结细菌移位率;盲肠内容物需氧菌总量和革兰阴性杆菌菌量;肠推进功能。结果：急性出血坏死性胰腺炎时外周血和门静脉血内毒素水平显著升高;肝、胰、肠系膜淋巴结组织细菌移位率显著升高;盲肠需氧菌总量和革兰阴性杆菌量显著升高;肠推进功能降低。应用茵陈蒿合承气汤能显著改善上述指标。结论：急性出血坏死性胰腺炎时存在细菌移位,茵除蒿合承气汤能有效地减少急性出血坏死性胰腺炎时细菌移位的发生。     

表皮生长因子对重症胰腺炎肠外营养大鼠肠道细菌易位的影响

探讨表皮生长因子（ＥＧＦ）对重症胰腺炎（ＳＡＰ）全肠外营养（ＴＰＮ）支持大鼠肠道细菌易位的影响。方法：４８只ＳＤ大鼠随机分为ＳＡＰ组、ＳＡＰ＋ＴＰＮ组及ＳＡＰ＋ＴＰＮ＋ＥＧＦ组。分别测定肠系膜淋巴结、肝脏及脾脏细菌易位率,利用图像分析仪对小肠粘膜进行检测,并测定回肠粘膜厌氧菌与需氧菌的比率。结果：ＳＡＰ＋ＴＰＮ＋ＥＧＦ组肠系膜淋巴结、肝脏及脾脏细菌易位率明显降低,小肠粘膜绒毛面积、高度、隐窝深度增加,回肠厌氧菌与需氧菌的比率显著提高。结论：ＥＧＦ具有保护重症胰腺炎全肠外营养大鼠肠粘膜机械屏障、生物屏障和降低肠道细菌易位率的作用。     

静脉注射内毒素法制作大鼠肠道细菌易位模型

目的探讨静脉注射内毒素制作大鼠肠道细菌易位模型的方法。方法60只雄性SD大鼠(体重200～250g)随机分为4组(15只/组)。其中3组为实验组,按组别不同分别给予尾静脉注射内毒素2、4、6mg/kg;对照组给予尾静脉注射生理盐水0.5ml。观察各组大鼠的体温、呼吸频率、外周血白细胞计数及死亡率,7d后将各组大鼠分别开腹取门静脉血、下腔静脉血、肠系膜淋巴结、肝、脾和胰腺组织作细菌培养。结果注射内毒素后各组大鼠的体温、呼吸频率及外周血白细胞均有不同程度的升高。2mg/kg组大鼠无死亡,组织细菌培养阳性率为24.4%。4mg/kg组的死亡率为20.0%,细菌培养阳性率为47.2%,其中肠系膜淋巴结阳性率为83.3%。6mg/kg组的死亡率为46.7%,细菌培养阳性率为64.6%,其中肠系膜淋巴结阳性率为100.0%。结论4mg/kg剂量的内毒素静脉注射是制作大鼠肠道细菌易位模型的较为理想可行的方法。     

The role of the gut in the development of sepsis in acute pancreatitis

The pathogenesis of sepsis in acute pancreatitis is unknown. Since the intestinal tract has recently been identified as a possible source for sepsis in other conditions, we explored whether the gut may serve as a reservoir for bacteria causing systemic and pancreatic infection in acute pancreatitis. Bacterial translocation, alterations of intestinal microflora, and intestinal motility, as reflected by gut propulsion, were studied in a rat pancreatitis model. Acute pancreatitis was induced by biliopancreatic obstruction (AP); sham manipulated animals served as controls (sham). Bacteriologic cultures were obtained from various segments of the intestinal tract and from blood, liver, spleen, pancreas, and mesenteric lymph nodes 48 and 96 hr after induction of AP or sham. Bacteria were recovered from mesenteric lymph nodes of all 12 animals with AP, but only from 3/14 sham animals (P less than 0.05). Spread to distant organ sites occurred in 4 of 12 animals with AP compared to none of the sham animals (P less than 0.05). A disruption of the intestinal microflora was found in the cecum, where the gram-negative bacterial count (log/g) was significantly higher during AP when compared with sham controls: 10.62 +/- 1.04 vs 8.05 +/- 1.45 at 48 hr and 7.92 +/- 0.62 vs 6.79 +/- 0.87 at 96 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of surgical trauma on the bacterial translocation from the gut.

Bacterial translocation is the passage of viable bacteria from the lumen of the gastrointestinal tract through the intestinal mucosa to other sites. It is believed that bacterial translocation may lead to infection and septicemia. The purpose of this study was to determine what factors in experimental surgical trauma lead to bacterial translocation. Two-month-old Wistar albino rats were divided into five groups: (A) control; (B) anesthesia (ether inhalation); (C) anesthesia and surgery (median laparotomy and transient compression of the intestines); (D) fasting only; and (E) anesthesia, surgery, and fasting. After 48 hours, ileum, mesenteric lymph nodes, and blood were cultured for aerobic and anaerobic organisms. In each group the number of animals with bacteria overgrowth was calculated. The incidence of bacterial translocation to mesenteric lymph nodes and blood in groups B and D were similar to the controls (P greater than .01). There was a significant increase in the number of animals with bacterial translocation in groups C and E (P less than .001). The majority of translocating bacteria were E coli.     

Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis

Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.     

Total parenteral nutrition promotes bacterial translocation from the gut

Bacterial translocation from the gut may be the primary event in many disease processes. The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut. Each of 90 female Fischer rats underwent placement of a central venous catheter and was randomized to one of three groups. Group I (control) received food and water ad libitum. Group II received standard TPN solution orally from a bottle sipper and drank the solution ad libitum. Group III underwent TPN via the central catheter by pair feeding of the animals with group II. Animals were fed for 2 weeks, and liver, spleen, mesenteric lymph nodes, blood, and cecum were aseptically obtained for culture. A statistically significant difference (p less than 0.014) was found between translocation rates of parenterally fed animals compared with enterally fed animals. Two thirds of the animals (18/27) fed parenterally had culture-positive mesenteric lymph nodes compared with one third (9/27) of the enterally fed group and none (0/30) of the control group. A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution, independent of route. Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense.     

Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis

BACKGROUND: Infection is the commonest cause of death in acute pancreatitis. Early reduction of commensal flora (particularly Lactobacillus species) and, at the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli, have recently been described during acute pancreatitis. Lactobacillus plantarum has been shown to be effective in reducing the egress of endotoxin and microbial translocation in several experimental models such as chemically induced hepatitis and ulcerative colitis. AIM: The aim of the study was to determine whether L. plantarum 299v (Lp 299v) is capable of effectively reducing microbial translocation in experimental pancreatitis. METHODS: Acute pancreatitis was induced by isolation and ligation of the biliopancreatic duct in Lewis rats weighing 250-350 g. The animals were divided into 3 groups: group A, sham operation; group B, induction of pancreatitis and no further treatment, and group C, induction of pancreatitis + daily administration by gavage of a 5-ml/day suspension of Lp 299v at 0.5-1.0 x 10(9) bacteria/ml for 8 days, 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 h. Histological studies and microbiological analyses were performed. RESULTS: At sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute pancreatitis was the specific disease investigated, only these animals were subjected to further study. In group B, we found pathogenic micro-organisms in the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in 10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus faecalis, Pseudomonas and Proteus species. In contrast, when the animals were kept under an 'umbrella' of Lp 299v, growth of E. faecalis or E. coli were detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic tissue cultures. CONCLUSIONS: Lp 299v is effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative to antibiotic therapy.     

N-acetylcysteine improves intestinal barrier in partially hepatectomized rats

BACKGROUND: Translocating enteric bacteria play an important role in the development of infections following partial hepatectomy. The intestine itself is the first line of defence against bacterial translocation (BT). We investigated the effect of N-acetylcysteine (NAC) on BT and the intestinal wall. METHODS: We compared four groups of Sprague-Dawley male rats (eight in each group): sham, sham plus preoperative single dose of NAC, partial hepatectomy and partial hepatectomy plus preoperative single dose of NAC. Microorganism count in the tissues and the glutathione and malondialdehyte contents of the intestinal wall were studied at the end of the 24th hour. RESULTS: Bacterial growth was observed in the spleen and mesenteric lymph nodes in the sham group. There was bacterial growth in all the samples of the partial hepatectomy group. Differences were significant except in atrial and portal blood counts. In the partial hepatectomy plus NAC treatment group, counts were significantly low in all, except atrial and portal blood samples. The malondialdehyte level in the intestinal wall was 35.38 +/- 10.27 in the sham group, increasing significantly in the partial hepatectomy group (69.50 +/- 21.48), and decreasing in the partial hepatectomy plus NAC treatment group (35.63 +/- 14.12). Glutathione levels decreased significantly in the partial hepatectomy group and increased with preoperative single-dose NAC. CONCLUSION: Partial hepatectomy resulted in oxidative disturbances in intestinal wall, which in turn gave rise to BT. Parenteral NAC protects the intestinal wall from oxidative injury and attenuates BT.     

选择性肠道去污染对肝硬化大鼠肝门阻断细菌移位、内毒素血症的影响

目的探讨选择性肠道去污染对肝硬化大鼠肝门阻断后肠道细菌移位、内毒素血症的效果。方法将制成肝硬化模型的60只雄性SD大鼠随机分为假手术组、肝门阻断30rain组（阻断组）及通过选择性肠道去污染预处理组（预处理组）,各20只。在实验术后30min及24h时分别取肠系膜淋巴结、肝、肺及门、腔静脉血作细菌培养,并取门、腔静脉血作内毒素检测。结果阻断组大鼠手术后30min即出现门、腔静脉血内毒素浓度升高（P〈0．01）,在手术24h后升高更明显。并在术后24h肠系膜淋巴结、肝组织及门、腔静脉血细菌培养出现阳性,主要为大肠杆菌。预处理组大鼠无论是手术30min还是24h后,门、腔静脉内毒素水平升高均不明显,较阻断组明显降低（P〈0．01）,肠道外组织及门、腔静脉血细菌培养阳性率也明显降低。结论肝硬化大鼠肝门阻断30min后早期即可出现内毒素血症,并于手术24h后出现明显肠道细菌移位。选择性肠道去污染能减少肝硬化大鼠肝门阻断后肠道细菌移位及内毒素血症的发生。     

Inhibition of nitric oxide production and the effects of arginine and Lactobacillus administration in an acute liver injury model.

OBJECTIVE: To study the effect of inhibiting nitric oxide production and the effects of arginine and lactobacilli administration in an acute liver injury (LI) model. SUMMARY BACKGROUND DATA: Infectious complications caused by enteric bacteria are common in patients with liver diseases and those who have undergone liver surgery. Increased bacterial translocation has been proposed as one underlying mechanism. Lactobacilli constitute an integral part of the normal gastrointestinal microecology; they are involved in host metabolism and have many beneficial properties. Arginine has numerous roles in cellular metabolism and may be metabolized by lactobacilli in some cases. We have previously shown that rectal administration of Lactobacillus plantarum DSM 9843 (strain 299v), with and without arginine, in an acute LI model significantly reduces the extent of the LI and reduces bacterial translocation. To clarify the pathogenetic mechanisms, we studied the role of nitric oxide in the effects of L. plantarum and arginine in acute LI, as determined by bacterial translocation, ileal, cecal, and colonic nucleotides, RNA, and DNA. METHODS: Male Sprague-Dawley rats were used. L. plantarum, 2% arginine, and/or N-nitro-L-arginine methyl ester (L-NAME), as appropriate, were administered rectally once daily for 8 days. Acute LI was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples were collected after 24 hours. Bacterial translocation was evaluated by culture of portal and arterial blood, mesenteric lymph nodes, and liver tissue. Liver enzymes and bilirubin were assayed in the serum. The bacterial load in the cecum and colon was determined. Ileal, cecal, and colonic mucosal nucleotides, RNA, and DNA were evaluated. RESULTS: The levels of liver enzymes and bilirubin were lower in liver-injured rats supplemented with arginine and Lactobacillus, and this effect was abolished by the addition of L-NAME. Inhibition of nitric oxide production (by L-NAME) increased bacterial translocation in many groups. L-NAME administration increased the cecal and colonic bacterial count and decreased the levels of mucosal nucleotides, RNA, and DNA. CONCLUSIONS: Inhibition of nitric oxide production modulated the effects of arginine and L. plantarum in this acute LI model. L-NAME potentiated the LI, as indicated by elevation of liver enzymes and bilirubin, and it also increased bacterial translocation and the cecal and colonic bacterial count. Increased bacterial translocation could be one of the mechanisms by which LI is potentiated.     

The Effects of Cefephim, G-CSF, and Sucralfate on Bacterial Translocation in Experimentally Induced Acute Pancreatitis

The preventive effects of granulocyte colony-stimulating factor, cefephim, and sucralfate on bacterial translocation in experimentally induced acute pancreatitis were investigated. Forty male Wistar albino rats were used in this study. For each rat, the pancreatobiliary ductus was ligated and hence acute pancreatitis was induced. In the control group, no further procedure was performed. Meanwhile, cefephim as an antibiotic, filgrastim, which is a colony-stimulating factor, and sucralfate were given to the other groups at the specified doses. To inhibit bacterial translocation by preserving the bowel barrier, sucralfate, which is known to have a cytoprotective effect on the gastrointestinal system, was used in high doses. Cefephim 30 mg/kg per day (intramuscularly) in group II, filgrastim 10 mg/kg per day (subcutaneously) in group III, and sucralfate 50 mg/kg per day by 8-F feeding tube gavage into the stomach in group IV were given. The number of bacteria translocated into the mesenteric lymph nodes, pancreas, liver, and spleen in the control group significantly increased in comparison with the other groups (P < 0.05). The average number of leukocytes (per mm³) in the control group was significantly higher than that of other groups (P < 0.0001). Regarding the average serum amylase levels, the values of all groups clearly decreased in comparison with the control group (P < 0.0001). Although in the cefephim, filgrastim, and sucralfate groups, (+) pancreatitis was generally seen, in the control group (+++) pancreatitis was detected. Bacterial translocation to the mesenteric lymph nodes and pancreas was partially prevented by filgrastim and sucralfate, and was completely prevented by cefephim. We conclude that in the management of acute pancreatitis, the use of the prophylactic antibiotics, sucralfate and filgrastim, may be advantageous. Received: July 2, 1999 / Accepted: September 26, 2000