Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats

Background The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat. Materials and methods Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection. Results Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8–25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not. Conclusions In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.     

Effect of early antibiotic prophylaxis with ertapenem and meropenem in experimental acute pancreatitis in rats

Background  The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat. Methods  Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection. Results  Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05). Conclusions  In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg⁻¹/day⁻¹). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN-supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

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.     

Pathogenesis and prevention of early pancreatic infection in experimental acute necrotizing pancreatitis.

OBJECTIVE: The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. BACKGROUND: Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. METHODS: Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. RESULTS: The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics. CONCLUSIONS: Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.     

Time course of bacterial infection of the pancreas and its relation to disease severity in a rodent model of acute necrotizing pancreatitis.

BACKGROUND: Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans. OBJECTIVE: The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis. METHODS: Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours. RESULTS: No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours. CONCLUSION: Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.     

Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

BACKGROUND: Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multispecies probiotics reduces bacterial translocation or improves outcome in a rat model of acute pancreatitis. METHODS: Male Sprague-Dawley rats were allocated into 3 groups: (1) controls (sham-operated, no treatment), (2) pancreatitis and placebo, and (3) pancreatitis and probiotics. Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Daily probiotics or placebo was administered intragastrically from 5 days prior until 7 days after induction of pancreatitis. Tissue and fluid samples were collected for microbiologic and quantitative real-time PCR analysis of bacterial translocation. RESULTS: Probiotics reduced duodenal bacterial overgrowth of potential pathogens (Log(10) colony-forming units [CFU]/g 5.0 +/- 0.7 [placebo] vs 3.5 +/- 0.3 CFU/g [probiotics], P < .05), resulting in reduced bacterial translocation to extraintestinal sites, including the pancreas (5.38 +/- 1.0 CFU/g [placebo] vs 3.1 +/- 0.5 CFU/g [probiotics], P < .05). Accordingly, health scores were better and late phase mortality was reduced: 27% (4/15, placebo) versus 0% (0/13, probiotics), respectively, P < .05. CONCLUSIONS: This experiment supports the hypothesis that modification of intestinal flora with multispecies probiotics results in reduced bacterial translocation, morbidity, and mortality in the course of experimental acute pancreatitis.     

N-乙酰半胱氨酸对大鼠急性坏死性胰腺炎胰腺损伤的影响

目的 探讨急性坏死性胰腺炎(ANP)胰腺损伤与核因子-κB(NF-κB)活化、胰腺细胞凋亡的关系及N-乙酰半胱氨酸(NAC)对胰腺损伤的影响.方法 33只Wistar大鼠分为正常对照、盐水对照和胰腺炎组.以3.5%牛磺胆酸钠逆行注入胰胆管制作ANP模型,于造模前、后1 h应用NAC,12 h后取材,采用凝胶电泳迁移率实验测定胰腺组织NF-κB活性、改良TUNEL法检测细胞凋亡.同时观察血淀粉酶、脂肪酶、胰腺组织湿/干重比率及病理改变. 结果盐水对照组NF-κB活性很低(2.00±0.33),胰腺炎组NF-κB明显活化(6.03±0.41),造模前使用NAC抑制NF-κB活性(3.28±0.42),降低淀粉酶及胰腺湿/干重比率,促进胰腺细胞凋亡(P<0.05).NF-κB活化与凋亡呈负相关(r=-0.96,P<0.01),与胰腺损伤病理呈正相关(r=0.63,P<0.01);胰腺损伤病理分级与凋亡呈负相关(r=-0.98,P<0.01).结论 NAC可能通过抑制胰腺NF-κB活化、促进胰腺细胞凋亡,减轻胰腺损伤.     

Endothelin receptor antagonists are not beneficial in the therapy of acute experimental pancreatitis

BACKGROUND AND AIM: Due to increased capillary permeability and the early appearance of vasoactive and toxic agents, patients suffering from necrotizing pancreatitis frequently develop a systemic inflammatory response syndrome (SIRS). Endothelin, a potent vasoconstrictor, is thought to play a major role in these changes via the regulation of microcirculation. An improved outcome of acute experimental necrotizing pancreatitis by blocking the endothelin receptors ETA and ETB, either selectively (only ETA) or unselectively (ETA and ETB), has been suggested. The aim of this study was to investigate further the beneficial effects of new, highly potent endothelin-receptor (ET-R) antagonists in acute experimental pancreatitis. METHODS: The influence of the selective ET-RA antagonist BSF208075 (1 mg/kg) on mortality was studied in three severity groups of acute necrotizing pancreatitis (retrograde injection of 4%, 5% and 6% of sodium taurocholate into the main pancreatic duct). The effects of the selective ET-RA antagonists LU135252 (LU13) and BSF208075 (BSF20) and of the unselective endothelin receptor (ET-R(A/B)) antagonist BSF420627 (BSF42) were additionally analyzed in 4% taurocholate-induced necrotizing pancreatitis. Furthermore, the significance of variable doses of the endothelin receptor antagonist LU13 (1 mg/kg, 3 mg/kg and 100 mg/kg) was determined in a 4% sodium taurocholate model and in a cerulein pancreatitis model. RESULTS: Prophylactic ET-R antagonism increased the mortality rate in the 4% sodium taurocholate-induced pancreatitis. No reduction in pancreatic damage after induction of taurocholate pancreatitis was found by ET-R blockage. Application of ET-R antagonists had no beneficial influence in ascites development. However, administration of LU13 (100 mg/kg) resulted in a non-significant increase in pancreatic oedema, whereas peritoneal necrosis was not affected. CONCLUSION: The selective and unselective ET-R antagonists BSF20, BSF42 and LU13 failed to improve survival and pancreatic damage during acute experimental pancreatitis. Therefore, previously reported beneficial effects of ET-R antagonists in experimental acute pancreatitis have to be critically evaluated before conclusions for further clinical development are made.     

急性胰腺炎大鼠TNF-α mRNA、IL-10 mRNA表达和胰腺细胞凋亡的研究

目的 探讨大鼠急性胰腺炎早期胰腺组织中TNF－αmRNA、IL－10mRNA的表达和细胞凋亡的变化规律。方法 以牛磺胆酸钠诱导20只大鼠急性水肿性胰腺炎（AEP）模型,20只急性坏死性胰腺炎（ANP）模型,另取10只正常大鼠作为对照。术后12h各处死10只大鼠,检测血清和胰腺组织中的TNF－α和IL－10水平,分析两者在胰腺组织中的mRNA较录水平,检测胰腺细胞的凋亡率。结果 正常、AEP和ANP组的细胞凋亡率分别为2．98％、17．29％和8．39％。制模后TNF－αm和IL－10增强ANP大鼠TNF－α表达增强。结论 急性胰腺炎大鼠胰腺组织中的TNF－α和IL－10的表达与其在血清和胰腺中的浓度成正比,胰腺本身可能就是产生细胞因子的主要器官。胰腺细胞凋亡率与疾病的严重程度呈负相关,凋亡是对胰腺损伤的良好反应。     

An experimental study on the role of beta-endorphin in the pathogenesis of acute pancreatitis and the effects and mechanisms of naloxone

120 SD rats were randomly divided into three groups: the sham operation group, the AP (acute pancreatitis) group, the naloxon treated group. AP was induced by intraductal injection of 5% sodium taurocholate solution. Naloxon was given intramuscularly at the dosage of 0.1 g/100 gw immediately after the injection and 90 minutes later. The survival rate and the mean survival time of the rats during 3 days after the induction of AP were determined. The pancreata were sampled for semiquantitative histopathologic evaluation. By using the fractional indicator distribution technique with 86 RB, QP/CO and pancreatic tissue perfusion performed 1 and 6 hours after the induction of AP, the amount of beta-endorphin in the hypothalamus and pituitary was measured 1 and 4 hours after the induction of AP. It was found in the naloxon treated group, the pancreatic blood flow and tissue perfusion was greatly increased, the mortality rate was decreased, and the rats survival time was significantly prolonged. The results suggest that: (1) The hemodynamic changes play an important role in the pathogenesis of AP. (2) Beta-Endorphin may play a role in the pathophysiological process of AP. (3) naloxon has good therapeutic effects on AP.     

Experimental acute necrotising pancreatitis: evaluation and characterisation of a model of intraparenchymal injection of sodium taurocholate in rats.

OBJECTIVES: To evaluate a simple model that produces progressive dose dependent pancreatitis, by intraparenchymal injection of sodium taurocholate. DESIGN: Open laboratory study. SETTING: Teaching hospital, Israel. MATERIALS: Forty eight Wistar rats. INTERVENTIONS: Sodium taurocholate was injected, 0.3 ml/100 g body weight, in concentrations of 5% and 10% into the pancreatic parenchyma of 32 Wistar rats, resulting in two distinct groups of severity. In 16 sham controls, saline was injected into the pancreas in similar fashion. Blood samples were withdrawn before, and 6, 24, 48, and 72 hours after induction of pancreatitis. RESULTS: Six hours after taurocholate injection, there was a sharp increase in the plasma activities of amylase, lipase, and lactate dehydrogenase (LDH). After 24 hours plasma activities of amylase and lipase decreased to near normal values while LDH remained slightly increased for 48 hours and decreased only after 72 hours. At 6 hours after the injection, interleukin-6 (IL-6) concentrations had increased slightly in the 5% group and decreased to the baseline values at 24 hours. In the 10% group, the increase in IL-6 values was significantly greater than in the 5% group (p = 0.04), and correlated well with severity of pancreatitis as defined by histology (p = 0.01) and mortality (p = 0.037). Twenty four hours after injection of taurocholate, morphological changes comprising diffuse necrosis of the pancreas, fat necrosis, and intestinal dilatation secondary to paralytic ileus were severe. Histopathological examination of the pancreas showed good correlation with the clinical findings and with mortality. No morphological changes were detected when saline was injected into the pancreas (sham control), and only mild rises of IL-6, lipase, amylase, and LDH activities were seen at 6 hours after injection. The mortality, after 10 days, was 80% in the 10% taurocholate group, 30% in the 5% taurocholate group, and 0 in the sham control group (p < 0.05). CONCLUSION: The intraparenchymal injection of taurocholate is easy to perform and highly reproducible. The histopathological injury is dose-dependent, as is the mortality. We conclude that this model is valuable for the study of new treatments for pancreatitis.     

Pancreatic capillary blood flow in an improved model of necrotizing pancreatitis in the rat

INTRODUCTION: The development of acute pancreatitis is characterized by profound changes in pancreatic microcirculation. Using in vivo microscopy with fluorescent-labeled erythrocytes as tracers we studied changes in pancreatic microcirculation in an improved rat model of necrotizing pancreatitis (NP) in comparison to edematous pancreatitis (EP) and healthy controls. METHODS: Twenty-one male Wistar rats had their pancreatae exteriorized in a temperature-controlled immersion chamber followed by intravenous administration of fluorescent-labeled autologous erythrocytes. EP was induced by intraductal saline and intravenous caerulein (5 microg/kg/h) for 6 h (n = 7) and NP by controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L) followed by intravenous caerulein (n = 7). Control animals received intraductal and intravenous saline (n = 7). The determination of pancreatic microcirculation was performed before as well as 1, 3, and 6 h after intraductal infusion by correlating the number of passing labeled erythrocytes/capillary/min with their concentration per microliter of arterial blood. RESULTS: Pancreatic capillary flow in control animals remained constant over the 6-h observation period. Pancreatic capillary flow in the EP group rapidly increased to 188% of baseline after 3 h and remained significantly elevated throughout the experiments (P = 0.0001). In contrast, pancreatic capillary flow decreased significantly in the group suffering NP with values 46.7% of baseline after 6 h (P = 0.0001). Complete capillary stasis developed in 38% of investigated capillaries in the NP group compared to 0-1% in both other groups (P = 0.0001). CONCLUSION: Pancreatic microcirculation in mild edematous pancreatitis is significantly increased while the evolution of necrotizing pancreatitis in the model studied herein is characterized by a dramatic reduction in pancreatic capillary flow in conjunction with areas of capillary stasis. These results underline the pathophysiologic relevance of the model and of therapeutic measures aimed at an improvement of pancreatic microcirculation in clinical necrotizing pancreatitis.     

环孢素A对大鼠急性出血坏死性胰腺炎脑损伤保护作用

目的探讨环孢素A在大鼠急性出血坏死性胰腺炎（ANP）时对脑组织损害的保护作用,从而为胰腺炎脑损伤的治疗提供实验依据。方法将60只SD大鼠随机分为正常对照组,诱导组和环孢素A处理组,经胰胆管逆行注射5％牛磺胆酸钠建立大鼠ANP模型,12h后处死动物,测定血清的TNFα水平,并检测脑组织含水量、脑组织MDA含量及脑微血管内白细胞聚集及附壁现象。结果经环孢素A处理后,血清中TNFα水平、脑组织含水量、脑组织MDA含量、脑微血管内白细胞聚集及附壁现象显著降低（P〈0．01）。结论环孢素A可以减轻脑损害的发生和发展。     

前列腺素E_1防治大鼠急性坏死性胰腺炎的作用及机理

研究前列腺素E_1防治大鼠急性坏死性胰腺炎的作用及其机理。方法:向大鼠胰管内注射5％牛磺胆酸钠溶液制成急性坏死性胰腺炎(ANP)模型。结果:ANP时,胰腺毛细血管通透性(PCP)明显增高,胰腺组织中性粒细胞过氧化酶(MPO)活性及脂质过氧化物(LPO)水平明显增高。病理示组织内大量PMN浸润、片状出血、坏死。PGE_1使PCP明显下降,MPO、LPO显著降低,动物存活明显改善结论:PGE_1通过抑制中性粒细胞(PMN)活化减少氧自由基(OFR)释放,减轻血管内皮细胞及胰腺组织损伤。     

The relative safety of MRI contrast agent in acute necrotizing pancreatitis.

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

雷公藤多甙联合生长抑素治疗对大鼠急性坏死性胰腺炎肠道细菌移位的影响

目的 探讨雷公藤多甙联合生长抑素治疗对大鼠急性坏死性胰腺炎(ANP)肠道细菌移位的影响. 方法 逆行胰胆管穿刺注射3.5%牛磺胆酸钠(0.2 ml/100 g)诱导ANP大鼠模型.分为5组:假手术组(SO)、坏死组(ANP)、生长抑素治疗组(ANP+S)、雷公藤多甙治疗组(ANP+T)、雷公藤多甙+生长抑素治疗组(ANP+T+S).术后禁食12 h,不禁水.各组均随机标记6只观察术后生存时间.术后24h,观察血清淀粉酶、血清脂肪酶活性,血浆内毒素水平,脏器细菌培养结果,胰腺和回肠黏膜病理学变化及大鼠存活率. 结果 雷公藤多甙与生长抑素联合治疗ANP大鼠,可以显著降低血清淀粉酶、血清脂肪酶活性;减轻胰腺组织和肠黏膜炎症细胞浸润、水肿;降低血浆内毒素水平和脏器细菌培养阳性率;提高ANP大鼠存活率. 结论 ANP大鼠存在肠道细菌移位;雷公藤多甙联合生长抑素的治疗可减轻ANP大鼠胰腺和肠道损伤,加强肠道的生物学屏障,降低肠源性细菌及内毒素移位发生率,阻止ANP的发展.     

急性坏死性胰腺炎大鼠血浆内皮素的改变及其意义

为了解急性坏死性胰腺炎（ａｃｕｔｅ ｎｅｃｒｏｔｉｚｉｎ ｐａｎｃｒｅａｔｉｔｉｓ,ＡＮＰ）时血浆内皮素（ｅｎｄｏｔｈｅｌｉｎ,ＥＴ）的变化及其病理意义,进行了前瞻性动物实验。即将ＳＤ大鼠随机分为３组：急性坏死性胰腺炎组（ＡＮＰ组,ｎ＝２）,组胆胰管注入５％牛磺胆酸钠（ＳＴＣ １ｍｌ／ｋｇ）制造ＡＮＰ模型,假手术组（ＳＯ组,ｎ＝２４）和血小板激活因子拮抗剂ＢＮ５０７３９组（ＢＮ组,ｎ＝２４）。测定     

Enzymatic and histological alterations in the isolated perfused rat pancreas in the taurocholate and cerulein model of acute pancreatitis]

METHODS: The pancreas of 24 male Wistar rats was perfused extracoporally by modified Krebs-Ringer-buffer for 80 minutes (including a 20 minutes equilibration period). To verify any organ damage we measured the activity of pancreatic enzymes like amylase, lipase and lactatdehydrogenase in the portal effluent. Furthermore histological changes were analysed after perfusion. Organ damage was induced by adding cerulein in a physiological dose (10(-10) M, n = 6) and in a supramaximal dose (10(-8) M, n = 6) and by intraductal injection of taurocholate (3.5 %, n = 6). RESULTS: Already 10 minutes after stimulation with cerulein (10(-8) M) and after intraductal injection of taurocholate increased activities (p < 0.01) of amylase and lipase were measured in the portal effluent compared to the group without any treatment. Lactatdehydrogenase levels did not changed. Apart from marked oedema in both groups considerable zones of necrosis could be noticed especially in the taurocholate group. CONCLUSION: Our data suggest that the isolated perfused rat pancreas (IPRP) is a valuable experimental tool to verify pathophysiological changes in the early phase of acute pancreatitis (AP). Various established models of AP such as by cerulein hyperstimulation or intraductal injection of taurocholate, could be applied to the IPRP. We conclude that this method enlarges the spectrum of established experimental models of acute pancreatitis.     

缺血-再灌注损伤对大鼠急性胰腺炎胰腺细胞凋亡的影响

目的探讨缺血一再灌注(I／R)损伤对大鼠急性胰腺炎(AP)胰腺细胞凋亡的影响。方法将SD大鼠54只按编号法随机分为对照组(n=6)、胰腺炎组(n=24)和I／R损伤组(n=24)。经胆胰管逆行加压注入3％牛磺胆酸钠建立大鼠AP模型，在此基础上，I／R损伤组通过暂时阻断脾下动脉造成局部胰腺I／R模型，对照组于术后lh，其余两组于术后1h、3h、6h和12h采取断颈方法分批处死动物，应用末端脱氧核苷酸转换酶(TdT)介导的原位末端标记(TUNEL)法检测缺血一再灌注区胰腺细胞凋亡。并观察其病理改变。结果胰腺炎组大鼠术后1h、3h胰腺组织仅为充血、水肿性改变，6h出现出血、坏死性改变；而1／R损伤组大鼠术后1h缺血一再灌注区胰腺呈现出血、坏死性改变，病变持续加重；AP后胰腺凋亡细胞明显增多，I／R损伤组和胰腺炎组的凋亡细胞高峰值分别在术后3h和6h；I／R损伤组术后1h、3h缺血一再灌注区胰腺凋亡细胞显著高于相应时相的胰腺炎组(P＜0．01，P＜0．05)．而6h、12h明显低于胰腺炎组(P＜O．05，P＜O．01)。结论I／R损伤在促发胰腺炎从水肿型向出血坏死型转化过程中，同时诱导胰腺细胞凋亡，细胞凋亡可能是阻止AP病变加重的一个有利反应。