【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 the etiology, symptoms, diagnosis, surgical treatment, and outcomes of acute necrotizing mediastinitis (ANM) in order to guide future diagnosis and treatment of ANM. Methods The clinical data of patients with ANM referred to West China Hospital, Sichuan University from March 2012 to April 2021 were retrospectively analyzed. The etiology, clinical manifestations, demographic characteristics, bacterial culture results, surgical approach and prognostic factors of these patients were summarized. ResultsA total of 176 patients were enrolled in this study. The median age was 60 ( 0-84) years. There were 124 (70.5%) males and 52 (29.5%) females. The most common origin of infection was neck (n=66, 37.5%). The most common symptom was fever (n=85, 48.3%). Streptococcus constellatus represented the most common pathogens in secretion culture. Surgical treatment was administered to 119 (67.6%) patients through different approaches, including 54 (30.7%) patients of cervical approach, 9 (5.1%) patients of thoracotomy, 18 (10.2%) patients of video-assisted thoracoscopic surgery (VATS), 7 (4.0%) patients of cervical combined with thoracotomy, 30 (17.0%) patients of cervical combined with VATS, and 1 (0.6%) patient of subxiphoid approach. Among this cohort, 144 (81.8%) patients were cured, while 32 (18.1%) patients died. Age-adjusted Charlson comorbidity index (OR=2.95, P=0.022), perioperative sepsis (OR=2.84, P=0.024), and non-surgical treatment (OR=2.41, P=0.043) were identified as independent predictors of poor outcomes. Conclusion For patients with corresponding history and manifestations of ANM, it is crucial to go through imaging examination to confirm the presence of an abscess and guide the selection of surgical approach. Once the diagnosis of ANM is made, it is imperative to promptly perform surgical intervention for effective drainage. Our study highlights the significance of age-adjusted Charlson comorbidity index, perioperative sepsis and surgical treatment in predicting patients’ outcomes.
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.
The purpose of the study was to observe effect of chinese medicine “Qing Yi Tang” on the repair of injury of intestinal mucosa in acute necrotizing pancreatitis (ANP). Dogs ANP model were induced by injection of 5% sodium taurocholate (0.5 ml/kg) with 3 000 u/kg trypsin into the pancreatic duct. Diamine oxidase and anylase activity in blood, protein and MDA levels of ileal mucosa were to be determined in ANP and after treatment of “Qing Yi Tang”. Intestinal permeability was also to be studied, LPS and bacteria translocation (BT) were obseved. All animals were sacrificed on day 7, the tissue of ileal mocosa was collected for histological and ultrastructural studies. The results showed that after treatment with Chinese medicine “Qing Yi Tang”, the injury of intestinal mucosa in ANP reduced. The length, height, area and protein of ileal mucosa increased significantly, intestinal permenbility decreased, the levels of LPS reduced in 1-2 times, and organ BT rate also reduce in 50%. The results indicated that chinese medicine “Qing Yi Tang” had good effect on improving repair of intestinal mucosa injury, protecting gut barrier function, reducing the incidence of LPS and bacteria translocation.
ObjectiveTo explore the effects of urinastatin(UTI) on microcirculation of extrapancreatic organs in rats with acute necrotizing pancreatitis(ANP). Methods A total of 48 rats were randomized into control group, ANP group and UTI group. The model of ANP was established by uniform injection of 5% sodium taurocholate solution under pancreatic capsule, only injection of normal saline in control group. Then the rats of UTI group were injected with UTI through the femoral vein, the rats of ANP group and control group were injected with normal saline. The blood flow of lung, kidney and distal small intestine was measured by radioactive biomicrosphere technique at 2 h and 6 h after ANP.ResultsCompared with the control group, the blood flow of lung, kidney and intestine was decreased significantly in the ANP group at the 2 h and 6 h after ANP （P＜0.05）, compared with the ANP group, the blood flow was increased significantly in UTI group （P＜0.05）. ConclusionMicrocirculation disorder is an important factor of the extrapancreatic organ damage in ANP, and UTI plays a protective role against microcirculation disorder of the extrapancreatic organ in 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.
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.
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.
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.