This prospective animal study was designed to investigate the changes of plasma endothelin (ET) levels in acute necrotizing pancreatitis (ANP). Sprague-Dawley rats were randomly devided into 3 groups: acute necrotizing pancreatitis (ANP) group in which ANP was induced by infusion of 5% sodium taurocholate (STC) into biliopancreatic duct, sham operation (SO) group and platelet activating factor antagonist BN50739 (BN) group. Blood levels of ET and platelet activating factor (PAF) were detected. Pancreatic microcirculatory blood flow was measured and pancreatic histological scores were evaluated. Results showed that the pancreatic microcirculatory blood flow in ANP group was decreased to a great extent immediatly after induction of ANP and soon began to rise slowly for 3 hours and again decreased steadily after that. The blood levels of ET, PAF and histological scores in ANP group were significantly higher than those in SO group. In BN group, the blood flow was significantly improved and the levels of blood ET, PAF and histological scores were all significantly lower as compared to those in ANP group. It is concluded that ischemia/ reperfusion is present in the initiation of acute necrotizing pancreatitis induced by STC in the rat. This leads to injuries of endothelial cells and increase in the production of ET and PAF. I/R lesions,and interaction of ET and PAF lead to a vicious circle, thus augmenting the pathological changes in the pancreas.
In the early stage of acute necrotizing pancreatitis (ANP) of experimental monkeys, the concentration of tumor necrosis factor (TNF) in blood was significantly increased. Stilamin could significantly reduce the level of TNF, decrease the mortality, and prolong the survival time of monkeys. The authors draw the conclusion that TNF is an important inflammatory media in the early stage of ANP. Stilamin can significantly inhibit the inflammatory process and has good effect in the treatment of ANP in experimental monkeys.
Objective To investigate the mechanism of dexamethasone in the treatment of acute necrotizing pancreatitis (ANP). Methods The ANP of 48 SD rats were induced by retrograde infusion of sodium taurocholate through biliopancreatic duct.After 30 minutes,the therapy group was administrated with dexamethasone at a dose of 0.2 mg/100 g alone. The control group was administrated with the same amount of 0.9% saline solution.At fourth hour and twelfth hour,8 rats of each group were sacrificed to examine the levels of serum tumor necrosis factor-alpha(TNFα) and serum amylase,to score the degree of pancreatic necrosis and to evaluate acinar cell apoptosis by in situ hybridization by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL). The survial period of 8 rats in each group were observed. Results In therapy group, the level of TNFα was (17.8±2.7) pg/ml and (8.5±1.6) pg/ml,the apoptosis index was （36.94±4.12）% and （ 32.79±3.31）%,the survival period was (33.4±21.5) h.While the control group with the indexes mentioned above were as follows: (53.6±18.7) pg/ml and (37.2±11.1) pg/ml ( P＜0.01),（4.37±1.24）% and （5.12±2.11）% （P＜0.01）,(14.6±5.7) h (P＜0.01) ,the histologic scoring for ANP between therapy group and control group was a significantly distinct (P＜0.01). Conclusion Dexamethasone can induce pancreatic acinar cell apoptosis in this model. Proper leves of TNFα may play an important role in regulating the apoptosis.Apoptosis can protect pancreas from necrosis in ANP.
ObjectiveThe changes of intestinal permeability and relationship of intestinal mucosa and bacterial translocation were studied in rat acute necrotizing pancreatitis (ANP) models.MethodsThe ANP models were made by injection of 5% sodium taurocholate 1.0 ml into pancreatic subcapsula.Then wistar rats were divided into four groups,control group (n=20),ANP group(n=22),treatment model group fed with lactose (n=22) and treatment model group fed with MgSO4 and antibiotic (n=22).After 72 hours,the experimental models were sacrificed.Tissues of pancreas,mesenteric lymph node, ascites were collected for microbiological study.The intestinal permeability was observed by lanthanum tracer.The blood samples were obtained from portal vein and ascites in order to assay the amount of amylase in serum.The pathologic lesions were found in the intestinal villus of the model group, including acute necrosis of intestinal mucosa,necrotichaemorrhage as well as enteroparalysis and a mass of haemorrhagic ascites.ResultsBacterial translocation of model group were markedly elevated than that of control (P＜0.05).There were statistically significant differences in bacterial translocation among three model groups （P＜0.05）.The pathologic lesions were found in the intestinal villus of the model group,including acute necrosis of intestinal mucosa,necrotichaemorrhage as well as enteroparalysis and a mass of haemorrhagic ascites.The lanthanum grain in clearance of intestinal cell of model group can be observed by eletron microscope.ConclusionThere is a severe gut barrier damage and injury in the intestinal mucosa,which lead to bacterial translocation from intestine as the source of pancreatic infection.Cleaning out enteric bacteria,improving intestinal movement and feeding with lactose could decrease bacterial translocation to treat and prevent acute necrotizing pancreatitis.
Nineteen cats were randomly divided into two groups, 7 cats (group A) recieved about 200 times spotty injections of total of 2 ml of 94% alcohol in pancreatic parenchyma and 12 cats (group B) underwent intraductal alcohoh, partial obstruction of the main pancreatic duct (MPD) and intraparenchymal alcohol. Acute necrotizing pancreatitis occurred in all of the experimental cats after operation. 2 cats in group A (28.6%) died within 48 hours postoperatively. 4 cats in group B (33.3%) died, among them, 3 within 48 hours and 1 died after 2 weeks. Morphological and functional recovery of the exocrine pancreas were found in all the 5 survivals in group A, while 8 cats in group B developed chronic pancreatitis 15 weeks after the operation. The above results show that simple pancreatic necrosis can be recovered after eliminating the etiological factors and if these factors, whatever is primary or secondary still exist and continue to damage the pancreas, chronic pancreatitis may develop.
In order to observe activity of tumor necrosis factor (TNF) in the serum, pancreatic histopathological damage, as well as their relationships in acute necrotizing pancreatitis (ANP), thirty five SD rats were randomly divided into 7 groups according to their sampling time with 5 in each group. ANP was induced by retrograde infusion of 5% sodium taurocholate through biliopancreatic duct in 6 experimental groups (Group B1～B6).Blood and pancreatic tissue samples were obtained at hour 0,0.5,2,4,6 or 8 respectively when the animals were sacrificed.Results showed that serum level of TNF activity rose significantly in Group B2,and reached the maximal value in Group B4.The pancreatic histopathological damage in ANP rats was getting worse along with time. Serum TNF activity had close relation to pancreatic histopathological score (r=0.63, Ｐ＜0.01),suggesting that serum TNF may play an important role in the process of deterioration of pancreatic tissue damage during ANP.
【Abstract】Objective To investigate therapeutic effect and mechanism of hyperbaric oxygen and ulinastatin respectively or combinatively used to treat acute necrotizing pancreatitis (ANP). Methods One hundred and twenty SD rats were divided into 6 groups randomly: group of normal control, group receiving sham operation, group of untreated acute necrotizing pancreatitis (ANP group), group of acute necrotizing pancreatitis treated with hyperbaric oxygen (HBO group), group of acute necrotizing pancreatitis treated with ulinastatin (ULT group), and group of acute necrotizing pancreatitis treated with combined hyperbaric oxygen and ulinastatin (HBO+ULT group). The rat model of acute necrotizing pancreatitis was established according to Aho HJ et al. Concentrations of amylase, TNFα, TXB2 and 6ketoPGF1α in blood were measured through ELISA or radioimmunoassay. Changes of pancreatic histopathology were investigated. SPSS 10.0 was used in statistical analysis. Results The concentrations of amylase, TNFα, TXB2 in the ANPtreated groups were significantly lower than those of ANP group (P＜0.01) except for 6ketoPGF1α and the levels of amylase and TNFα of HBO group were strikingly higher than those in HBO+ULT group. Only the level of AMS was significantly different between ULT group and HBO+ULT group (P＜0.01). Pancreas histopathological scores(HS) and CD8 counts of ANP group were significantly higher than those the other three group, but CD4 counts and CD4/CD8 ratio were on the contrary (P＜0.05). HS of HBO and ULT were strikingly higher than those of HBO+ULT (P＜0.05).Conclusion ①Hyperbaric oxygen or ulinastatin can effectively decrease the blood levels of enzymes and cytokines and improve the pancreatic immunity. ②Hyperbaric oxygen in combination with ulinastatin are more effective than either of them in the treatment of ANP.
Objective To investigate protective effect of apocynin, the inhibitor of NADPH oxidase Ⅱ (NOX2), on lung injury induced by acute necrotic pancreatitis (ANP) in rat. Methods Forty SPF adult male Wistar rats were randomly divided into 4 groups: shame operation group (SO group, n=10), ANP model group (ANP group, n=12), apocynin treated group (APO group, n=10), and apocynin control group (APO-CON group, n=8). The ANP models were induced by the retrograde injection of 5% sodium taurocholate through the biliopancreatic duct in the ANP group and the APO group. The apocynin was injected at 30 min before the induction of ANP models in the APO group. The pancreas and duodenum of rats were just flipped and the apocynin and the 10% DMSO (2 mL/kg) were injected in the APO-CON group and SO group respectively. All the rats were sacrificed at 12 h after the operation. The blood samples were collected by the inferior vena cava puncture, and the levels of serum amylase and lipase were measured by the auto-chemistry analyzer. The lung tissues were harvested and the integrated optical densities (IODs) of the nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and NOX2 were detected by the immunohistochemistry assay. The IODs of the myeloperoxidase (MPO), Toll like receptor 4 (TLR4), and CD68 were detected by the immunofluorescence assay. The concentration of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were tested by the ELISA method. Results The levels of the serum amylase and lipase and the IODs of the NF-κB, TNF-α, NOX2, MPO, TLR4, CD68, and concentration of MDA of the lung tissues in the ANP group were significantly increased as compared with the SO group (P<0.05), these indices in the APO group were significantly decreased as compared with the ANP group (P<0.05). The SOD activity of the lung tissue in the ANP group was significantly decreased as compared with the SO group (P<0.05), which in the APO group was significantly increased as compared with the ANP group (P<0.05). Conclusion Apocynin can ameliorate lung injury induced by ANP through inhibiting activity of NOX2.
摘要:目的：探讨急性重症胰腺炎（SAP）早期不同种类液体复苏对其预后的影响。方法：应用随机对照的方法,分别对2007年12月~2009年10月同期入院的48例SAP患者,随机分成两组,试验组和对照组。试验组第一周内液体复苏采用晶体液和人工胶体（羟乙基淀粉）,对照组采用晶体液,其他治疗方法不变。然后统计其第一周死亡率、ARDS、多器官功能障碍综合征（MODS）发生率,对比两组患者呼吸频率、血氧饱和度和红细胞压积（HCT）差异,以及两组患者肠功能恢复时间、住院时间以及并发症发生率。结果：试验组的液体复苏较对照组显著改善SAP的各项指标（P＜005）。血清乳酸水平（15±05）mmol/L,红细胞压积(HCT)为（324±69）%,ScvO2为（817±152）%,病死率83%,MODS发生率333%,〖HT5”H〗结论:〖HT5”SS〗 SAP早期联合应用晶胶体进行液体复苏可有效恢复循环血容量和防止体液潴留,显著提高其治愈率。Abstract: Objective: To investigate the optimal strategy of fluid resuscitation in the early stage ofsevere acute pancreatitis.〖WT5”HZ〗Methods:〖WT5”BZ〗Fourfyeighs SAP patients who received treatment in our hospital from 12,2007 to 10,2009 were randomly divided into 2 groups (n=24) according to the different amounts of crystal and colloid inthe daily resuscitation,including crystal group,combined group(the ratio of crystal to colloid was 2 to 1).The levels of hematocrit(HCT),saturation of central vein oxygen ( ScvO2 ),serum lactic acid as well as the advent of negative fluid balance the amount of fluid contained in the third space,mortality rate and the incidence of multiple organ dysfunction syndrome(MODS) in different groups were compared.〖WT5”HZ〗Results:〖WT5”BZ〗 Compared with crystal group,all the parameters were significantly improved in combined group(P＜005).HCT in the group of patients was(324±69)%,ScvO2 was (817±152)%,lactic acid was(15±05)mmol/L,mortality rate was 83% and MODS incidence was 333%. Conclusion:In the early stage of SAP,fluid resuscitation by a combination of crystal and colloid could effectively restore blood volume, reduce the amount of fluid contained in the third space and significantly improve the prognosis of SAP.