【Abstract】Objective To study the influence of early hemofiltration on plasma concentrations of proinflammatory cytokines TNF-α and IL-1β and their transcription levels in severe acute pancreatitis (SAP) pigs. Methods The model of SAP was induced by retrograde injection of artificial bile into pancreatic duct in pigs. Animals were divided randomly into two groups: SAP hemofiltration treatment group (HF group, n=8) and SAP no hemofiltration treatment group (NHF group, n=8). TNF-α and IL-1β plasma concentrations were measured by ELISA. Their transcription levels in the tissues of pancreas, liver and lung were assayed by semi-quantitative reverse transcription polymerase chain reaction. Results After hemofiltration treatment, the plasma concentrations of TNF-α and IL-1β increased gradually but were lower than those of NHF group at the same time spot 〔at 6 h after hemofiltration treatment, (618±276) pg/ml vs (1 375±334) pg/ml and (445±141) pg/ml vs (965±265) pg/ml, P＜0.01〕. At 6 h after hemofiltration treatment, the transcription levels of TNF-α and IL-1β in tissues of pancreas, liver and lung were lower than in NHF group (57.8±8.9 vs 85.7±17.4, 48.0±8.1 vs 78.1±10.2, 46.2±9.6 vs 82.4±10.5; 55.9±9.0 vs 82.2±15.7, 40.6±9.2 vs 60.0±10.6, 35.7±9.8 vs 58.1±9.3, P＜0.01). Conclusion Early hemofiltration can reduce TNF-α and IL-1β plasma concentrations and transcription levels in SAP pigs.
Objective To investigate the expression of cyclooxygenase-2 (COX-2) in liver tissue of severe acute pancreatitis (SAP) rats. Methods A rat model of SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the biliary-pancreatic duct. Eighty rats were randomly divided into SAP group and control group. The levels of serum amylase (AMY), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF) -α and ascites AMY were detected dynamically at 4 h, 8 h, 16 h and 24 h after operation. The pancreatic and liver injuries were observed by light microscope. The expression of COX-2 in liver tissue was measured by immunohistochemistry. Results Compared with the control group, the levels of serum AMY, ALT, AST, TNF-α and ascites AMY increased significantly at the time point of 4 h, 8 h, 16 h and 24 h (Plt;0.05). These changes were paralleled with the histopathological changes of pancreatic and liver tissue. The expression positive rates of COX-2 at the different time in the SAP group were higer than those of the control group (Plt;0.05). There was a significantly positive correlation between the expression of COX-2 and ALT (rs=0.949, P=0.039), AST (rs=0.972, P=0.016) and serum AMY (rs=0.944, P=0.041), respectively. Conclusion Overexpression of COX-2 may play an important role in liver injury during SAP.
ObjectiveTo evaluate the therapic efficacy for severe acute pancreatitis (SAP) during different periods. MethodsAccording to internalized standard, 234 patients with SAP admitted to this hospital from January 1986 to October 2009 were included, which were divided into two stages based on the time of admitting to this hospital. The first stage named prior operation group was from January 1986 to August 1998 (n=117), the second stage named individual treatment group was from September 1998 to October 2009 (n=117). There was comparability in demography and clinic between two groups. The prior operation group primarily underwent laparotomy and medication, and the individual treatment group underwent multiple combined therapies. These indexes were compared between two groups: hospital stay, cure rate, and mortality; the incidences of pancreatic pseudocyst, pancreatic and peripancreatic abscess, pancreatic encephalopathy, cardiac insufficiency, acute renal failure (ARF), acute respiratory distress syndrome (ARDS), and shock. The efficacies for early treatment, ascites, biliary pancreatitis, and pancreatic and peripancreatic complications were compared two groups by stratified analysis. ResultsCompared with the prior operation group, the hospital stay was shorter (Plt;0.05), cure rate was higher (Plt;0.001), and mortality was lower in the individual treatment group (Plt;0.001). During the treatments, the incidences of pancreatic pseudocyst, pancreatic and peripancreatic abscess, pancreatic encephalopathy, cardiac insufficiency, ARF, ARDS, and shock in the individual treatment group were lower than those in the prior operation group (Plt;0.05). According to the stratified analysis, the efficacies for early treatment, ascites, biliary pancreatitis, and pancreatic and peripancreatic complications in the individual treatment group were better than those in the prior operation group (Plt;0.001). ConclusionIn recent years, the change of therapeutic mode significantly improves the treatment efficacy for SAP.
ObjectiveTo explore effect of α-adrenoceptor on modulating water of lung in severe acute pancrea-titis (SAP) rat. MethodsThe SD rats were randomly divided into sham operation group (n=5) and SAP group,the SAP group was divided into subgroups of SAP-4 h (n=5) and SAP-24 h (n=5).SAP model was made by injecting taurocholate into bilopancreatic duct.The wet-to-dry ratio,alveolar fluid clearance (AFC),and AFC affected by α1-adrenoceptor inhibitor-prazosin and α2-adrenoceptor inhibitor-yohimbine separately or together were measured in the lungs.The α1-adrenoceptor and α2-adrenoceptor mRNA expressions in the lungs tissues were measured by real-time PCR. Results① The wet-to-dry ratios in the SAP-4 h group and SAP-24 h group were obviously decreased as compared with the sham operation group (P<0.05),which in the SAP-24 h group was significantly lower than that in the SAP-4 h group (P<0.05).② The AFCs in the SAP-4 h group and SAP-24 h group were obviously increased as compared with the sham operation group (P<0.05).The AFCs in the SAP with α1-adrenoceptor inhibitor-prazosin or α2-adrenocpetor inhibitor-yohimbine or prazosin combined with yohimbine were all obviously decreased as compared with the SAP group (P<0.05).③ The α1 adrenoceptor and α2 adrenoceptor mRNAs in the SAP-4 h group and SAP-24 h group were obviously increased as compared with the sham operation group (P<0.05). ConclusionAFC might be modulated by α-adrenoceptor in SAP rat.
Objective To evaluate the effectiveness and safety of total enteral nutrition (TEN) versus total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP). Methods The databases such as Pubmed (1996 to June 2011), EMbase (1984 to June 2011), Cochrane Central Register of Controlled Trials of The Cochrane Library (Issue 6, 2011) and CBM (1978 to June 2011) were electronically searched, and the relevant references of the included papers were also manually searched. Two reviewers independently screened the trials according to inclusion and exclusion criteria, extracted the data, and assessed the methodology quality. Meta-analyses were performed using the Cochrane Collaboration’s RevMan 5.1 software. Results Seven randomized controlled trials (RCTs) involving 379 patients with SAP were included. The results of meta-analyses showed that compared with TPN, TEN could significantly reduce the risk of mortality (RR=0.33, 95%CI 0.20 to 0.55, Plt;0.000 1), pancreatitis-related infections (RR=0.35, 95%CI 0.25 to 0.50, Plt;0.000 01), required rate of surgical intervention (RR=0.43, 95%CI 0.23 to 0.82, P=0.01), and incidence of multiple organ failure (MOF) (RR=0.28, 95%CI 0.17 to 0.46, Plt;0.000 01). There was no significant difference in the nutrition strategies associated complications between TPN and TEN (RR=1.16, 95%CI 0.42 to 3.22, P=0.78). Conclusion Meta-analyses show that compared with TPN, TEN can reduce the risk of mortality, pancreatitis-related infections, required rate of surgical intervention, and incidence of MOF; and it will not increase the nutrition strategies associated complications. Consequently, TEN should be considered a better choice for SAP patients as early as possible.
ObjectiveTo study the effects of continuous regional arterial infusion (CRAI) of dexamethasone on plasma inflammatory factors of severe acute pancreatitis (SAP) rabbits. MethodsTwentyfour rabbits were randomly divided into sham operation group, SAP group, intravenous infusion of dexamethasone group and CRAI of dexamethasone group (each group 6 rabbits) by random number table. The serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and amylase (AMY) levels in rabbits were tested at hour 0.5, 3, 6, 9, and 12 after modeling succeed. The pathological changes of pancreas and the survival were observed on day 3 after modeling succeed. ResultsCompared with the sham operation group, the serum levels of IL-6 significantly increased at 3 h and reached the peak at 6 h, decreased at 9 h (all Plt;0.05); levels of IL-10 significantly increased at 6 h, continuously elevated at 9 h and 12 h (all Plt;0.001); levels of TNF-α significantly increased at 0.5 h (Plt;0.001), reached the peak at 6 h (Plt;0.001) and decreased at 9 h (Plt;0.05); levels of AMY significantly increased at 9 h, continuously elevated at 12 h (all Plt;0.05) in the SAP group. Compared with the SAP group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h, 9 h, and 12 h (Plt;0.001); levels of IL6 significantly decreased only at 6 h in the intravenous infusion of dexamethasone group; levels of TNF-α in the CRAI of dexamethasone group significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001), which in the intravenous infusion of dexamethasone group significantly decreased only at 6 h (Plt;0.05); levels of AMY in the CRAI of dexamethasone group and intravenous infusion of dexamethasone group all significantly decreased at 12 h (Plt;0.05). Compared with the intravenous infusion of dexamethasone group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h (Plt;0.05) and 12 h (Plt;0.001); levels of TNF-α all significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001); levels of AMY were not significantly different (Pgt;0.05). The pathological changes of pancreas in the CRAI of dexamethasone group were obvious, the death of rabbits reduced on day 3 after modeling succeed. ConclusionCRAI dexamethasone can effectively reduce the systemic inflammatory response and pancreatic inflammation, and reduce mortality.
ObjectiveTo evaluate the efficacy of intravenous glutamine on patients with severe acute pancreatitis. MethodsThe Cochrane Library, PubMed, EMbase, CNKI and CBM databases were searched up to January 2013. Randomized controlled trials (RCTs) that compared non-glutamine nutrition with intravenous glutamine supplemented nutrition in patients with severe acute pancreatitis were included. A method recommended by the Cochrane Collaboration was used to perform a meta-analysis of those RCTs. ResultsFour RCTs involving a total of 190 participants were included. Analysis of these RCTs revealed the presence of statistical homogeneity among them. Results showed that glutamine dipeptide had a positive effect on reducing the mortality rate[OR=0.26, 95%CI (0.09, 0.73), P=0.01], length of hospital stay[WMD=-4.85 d, 95%CI (-6.67, -3.03) d, P<0.001], and the rate of complications[OR=0.41, 95%CI (0.22, 0.78), P=0.006]. No serious adverse effects were found. ConclusionCurrent best evidence demonstrates that glutamine is effective for severe acute pancreatitis. Further high quality trials are required and parameters of nutritional condition and hospital cost should be considered in future RCTs with sufficient size and rigorous design.
Objective To explore and summarize the application of minimally invasive technique to every stage of severe acute pancreatitis (SAP). Methods The treatment of 101 SAP patients admitted to our hospital between January 1995 and December 2008 were retrospectively analyzed. After calculi were removed by endoscopic retrograde cholangiopancreatograpy (ERCP) and endoscopic sphincterotomy (EST), endoscopic nasobiliary drainage (ENBD) were applied, then rhubarb liquid was perfused into gut with a nutrient canal and ultrasound-guided abdominal drainage tube were simultaneously placed at the early stage. Some patients received continuous renal replacement therapy (CRRT) at the same time. Laparoscopic cholecystectomy (LC) was performed at the subacute stage, and choledochoscope was introduced to remove parapancreatic necrotic tissues at the late stage of SAP.Results Of all the 101 cases treated by the method mentioned above, 75 cases received ERCP (or EST) and ENBD, and 31 cases underwent rhubarb liquid perfusion with a nutrient canal. Eight cases underwent continuous renal replacement therapy (CRRT). Forty-eight cases underwent LC and ultrasoundguided abdominal drainage. Thirtysix cases with infected peripancreatic tissue or abscess underwent debridement under choledochoscope 3 to 14 times at the later stage. Five cases died of multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS). The hemobilia ocurred in 2 patients during choledochoscopy and was cured under direct visualization by electric coagulation. Intestinal fistula happened in 3 cases and cured by drainage. Pancreatic pseudocyst was latterly seen in 3 cases and treated by the anastomosis of cyst with jejunum through selective operation. After the hospitalization of 9-132 d (mean 24 d), 96 cases completely recovered. Conclusion Timely application of minimally invasive technique to every stage of SAP can avoid the defects of traditional operations, decrease the injury and interference to the maximum, and raise the cure rate.
Objective To establish a modeling method for an animal model simulating the decline of digestive function after a large amount of tissue necrosis of the pancreas due to acute injury after severe acute pancreatitis (SAP). Methods Twenty male SD rats were randomly divided into the model group and the sham operation group according to the random number table method, with 10 rats in each group. First, the SAP model was established by retrograde bile duct injection of sodium taurocholate in the model group, whereas the sham operation group received physiological saline injection. Fluid infusion began 2 hours later, twice a day, with an 8-hour interval, for 2 days. The traditional Chinese medicine Dachengqi Decoction without Decoction Granules was formulated into a suspension in proportion and administered by gavage once at 18 hours and once at 24 hours after the operation to ensure the blood volume of rats and reduce inflammatory damage. Normal drinking water was allowed 48 hours after modeling. After 72 hours, ordinary feed was given for feeding. The feeding lasted for 14 days (the total duration of the experiment was 17 days). The body weight, vitality status and stool characteristics of the rats were observed and recorded on the day of open feed feeding and 14 days later. Fourteen days after feeding, the animals were sacrificed and samples were collected for examination of blood glucose, fecal elastase and hematoxylin-eosin staining pathological scores. Results All 10 rats in the model group were successfully modeled with a 100% survival rate. The body weight of rats in the model group 14 days after ordinary feeding was lower than that on the day of open diet [(180.80±4.39) vs. (222.90±6.14) g, P<0.001], and lower than that of rats in the sham operation group 14 days later [(180.80±4.39) vs. (221.70±7.45) g, P<0.001]. Compared with the sham operation group, inflammatory cell infiltration injury still existed in the pancreatic tissue of the model group, and some pancreatic tissues showed pathologically related changes of chronic injury. The pathological score of the model group was higher than that of the sham operation group [7.5 (7, 9) vs. 0 (0, 0), P<0.001]; the blood glucose concentration increased [(13.000±1.531) vs. (8.070±0.851) mmol/L, P<0.001]. The secretion of fecal elastase, a metabolite of trypsin in vivo, was significantly decreased [(5.451±0.936) vs. (8.593±1.105) mg/mL, P<0.001]. Conclusion The use of short-term liquid supplementation, traditional Chinese medicine anti-inflammatory treatment, and early dietary stimulation can effectively combat early severe inflammatory damage in SAP, protect the life of model rats, and enable them to survive and experience digestive dysfunction, thus establishing an experimental animal model of digestive dysfunction in the late stage of SAP.
Objective To observe the influence of resveratrol on superoxide dismutase (SOD), malondialdehyde (MDA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) of intestinal mucosal ischemia-reperfusion injury protection in rats with severe acute pancreatitis (SAP). Methods Fifty-four rats were divided into three groups randomly: sham operation group (SO group), SAP model group (SAP group) and resveratrol-treated group (Res group). SAP model was made by injecting sodium taurocholate 50 mg/kg to pancreatic bile duct and resveratrol was given intravenously at 5 min after inducing SAP model. The rats were sacrificed at 3 h, 6 h and 12 h after inducing SAP model respectively by equal number. The levels of MDA, SOD, ICAM-1 and VCAM-1 and histological changes of small intestine were measured. Results The level of MDA in small intestine tissue in SAP group was significantly higher than that in SO group (P＜0.05), while the activity of SOD was significantly lower in the relevant tissues (P＜0.05). The expressions of ICAM-1 and VCAM-1 in SAP group were higher than those of SO group (P＜0.05). The activity of SOD in small intestine tissue in Res group was significantly higher than that in SAP group (P＜0.05); while the level of MDA was significantly lower in the relevant tissues (P＜0.05). The expressions of ICAM-1 and VCAM-1 in Res group were lower than those of SAP group (P＜0.05). Conclusions Oxygen free radicals are concerned with the process of pathological changes in intestinal mucosal ischemia-reperfusion in rats with SAP. Resveratrol might increase SOD activity and decrease MDA level to attenuate lipid peroxidation in small intestine of SAP, and reduce the expressions of ICAM-1 and VCAM-1 in intestine, thus diminish the damage of the intestine in SAP. And it acts as a protective effect to small intestinal ischemia-reperfusion injury.