Objective To investigate the changes of expression of zonula occludens-1(ZO-1) in rats with severe acute pancreatitis (SAP), and to study the relationship between the ZO-1 protein and microvascular injury in rats with SAP. Methods Forty-eight Wistar rats were randomly divided into sham-operation (SO) group and SAP group, each group enrolled 24 rats. Pancreas of rats in SO group were flipped only after laparotomies, but rats of SAP group were injected with 5% sodium taurocholate by retrograding cholangiopancreatography micro pump to produce the SAP model. At 6, 12, and 24 hours after operation, 8 rats were sacrificed to get abdominal aortic blood for testing the levels of peripheral blood amylase, trypsin, interleukin-8(IL-8), tumor necrosis factor-α(TNF-α), and ZO-1 protein. At the same time, pancreatic tissues were got to perform HE staining and immunohistochemical staining for observation of the pathological changes and the expression of ZO-1 protein respectively. Results Compared with SO group at the same time, the levels of peripheral blood amylase, trypsin, IL-8, TNF-α, and ZO-1 protein were all higher in SAP group (P < 0.05). The level of amylase in SAP-24 hours group was higher than those of 6 hours group and 12 hours group(P < 0.05), the levels of trypsin, IL-8, and ZO-1 protein in SAP group increased over time (P < 0.05), but levels of TNF-αin 3 time points of SAP group did not differ with each other significantly(P > 0.05). Results of regression showed that in the SAP group, the level of ZO-1 protein in serum was significantly positive correlated with pathological score of pancreatic tissue(b=0.96, P < 0.05), levels of serum amylase(b=0.87, P < 0.05), trypsin(b=0.72, P < 0.05), and serum IL-8 (b=0.69, P < 0.05), but was not significantly correlated with level of TNF-α(P > 0.05). HE staining results showed that damage of pancreatic tissues became worse over time in SAP group, and the pathological score of SAP-6 hours group was lower than those of 12 hours group and 24 hours group (P < 0.05). Immunohistochemical staining results showed that, in SAP group, with the extension of time, the number of ZO-1 protein granules in pancreatic acinar cells and capillary wall reduced, and expressed in capillaries discontinuously. Conclusion During the course of SAP, the concentration of serum ZO-1 protein increase, but its expression in the pancreatic tissue degrade, which is closely associated with microvascular injury and progression of pancreatic tissues.
Objective To investigate the mechanism of gastrointestinal motility disorder of severe acute pancreatitis （SAP） in rats. Methods SD rats were randomly divided into 2 groups：sham operation （SO） group （n=16） and SAP group （n=16）. The gastric antrum interdigestive myoelectric complex （IMC） of rat was recorded by using bipolar silver electrode recording， the concentration of serum motilin （MTL） and vasoactive intestinal peptide （VIP） were detected by enzyme-linked immunosorbent assay （ELISA） method， and determined the pancreatic pathology score. Results Compared with SO group， the concentration of serum MTL obvious decreased and the concentration of VIP obvious rised in SAP group （P＜0.01）. Compared with SO group， the time of IMC cycle， andⅠand Ⅱ phase were extended， and time of Ⅲ phase was shortened， also the amplitude and frequency of peak electric of Ⅲ phase were declined in SAP group （P＜0.01）. And the concentration of MTL in SAP group showed positive correlation with the time of Ⅲ phase of IMC （r=0.967， P＜0.01）， the concentration of VIP in SAP group showed negative correlation with the time of Ⅲ phase of IMC （r=-0.592， P＜0.05）. The pancreatic organization pathological score in SAP group was higher than that in SO group （P＜0.01）. Conclusion There is gastrointestinal motility disorder in SAP rats， furthermore， it may induce gastrointestinal motility disorder through effecting the gastrointestinal smooth muscle electrical activity.
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.
This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n=10) and the experimental group (n=14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08±1.29, 11.04±7.55 and 12.21±4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72±3.58, P < 0.01), while the Lactobacillus number was decreased significantly (0.67±0.34, P < 0.01), and the Bifidobacterium number was also decreased (4.59±3.42, P < 0.05) in the experimental group, so the ratio of Bifidobacterium/Escherichia coli was reversed. Besides, in the experimental group, the plasma endotoxin positive rates and the bacterial translocation rates were much higher (P < 0.01 or P < 0.05) and the pathology scores of pancreas and small intestines were also significantly higher (P < 0.01) than those in the control group. These results indicated that in severe acute pancreatitis rats, the intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.
Objective To investigate the effects of ginkgo biloba extract （GBE） on expressions of IL-1β, IL-6,and TNF-α in the pancreas and brain tissues of rats with severe acute pancreatitis （SAP）, and further to explore the pathogenesis of SAP and the efficacy of GBE on brain injury. Methods Fifty-four Winstar rats were randomly divided into normal control group, model group, and treatment group, with 18 rats for each group. For rats in the normal control group, only conversion of pancreas was performed by abdomen opening , followed by wound closure immediately. For rats in the model group and treatment group, 5% sodium taurocholate hydrate were injected under pancreatic capsule to establish SAP model, and then GBE and normal saline were infected into intra-abdomen repeatedly every 8 hours, respectively. At 6 h, 12 h, and 24 h after the model establishment, experimental samples were extracted and serum amylase was detected. Pathogenic scoring for pancreas tissues was performed under light microscopy, and immunohistochemistry method was employed to detect the expression levels of IL-1β, IL-6, and TNF-α in pancreas and brain tissues. Results For the treatment group, both serum amylase and pancreas scoring were significantly lower than those of the model group （P＜0.01）. At 24 h after model establishment, the expressions of IL-1β, IL-6, and TNF-α of pancreas tissues in model group were significantly higher than those at 6 h and 12 h （P＜0.05 or P＜0.01）, but no significant differences wereobserved in treatment group （P＞0.05）. The expressions of IL-1β, IL-6, and TNF-α of brain tissues in model group were significantly higher than those at 6 h and 12 h （P＜0.05 or P＜0.01）, but in treatment group decreased （P＜0.05 or P＜0.01）. The expressions of IL-1β, IL-6, and TNF-α in the treatment group were significantly lower than those of the model group at same time （P＜0.01）. Conclusions During SAP, the expressions of IL-1β, IL-6 and TNF-α in pancreas and brain tissues increased obviously. GBE showed suppressing and scavenging effects on IL-1β, IL-6 and TNF-α in pancreas and brain tissues.
Objective To investigate the mechanism of radix salviae miltiorrhizae (RSM) injection in treatment of pancreatitis through observing the changes of activity of nuclear factor-kappa B (NF-κB) in pancreas of rats with severe acute pancreatitis (SAP) and the influence of RSM injection upon NF-κB in pancreas tissue. Methods Seventy-five rats were randomly divided into 3 groups: normal control group, SAP group and RSM treatment group, which were injected with normal saline, normal saline or RSM in the peritoneal cavity, respectively. The model of SAP rats was made by injecting L-arginine into peritoneal cavity and by subcutaneous injection at the same time. The concentrations of amylase in plasma and in ascites were measured respectively, and the expression of NF-κB in pancreas tissues was determined by immunohistochemistry. Results The levels of amylase in plasm and ascites in SAP group and RSM treatment group increased significantly with the increased expression of NF-κB in pancreas tissue, but it was also found that both the level of amylase and the expression of NF-κB in RSM treatment group were significantly lower compared with those in SAP group, and the survival time of RSM treatment group was longer than SAP group with less pathological injury in the pancreas tissues. Conclusion RSM may be effective for the treatment of pancreatitis by degrading the expression of NF-κB.
Objective To investigate the protective effect of castanospermine (CS) on renal injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group, n=8), SAP group (n=8), and CS group (n=8). SAP models were induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in the SAP group and the CS group. CS solution (200 mg/kg) was immediately administered via intraperitoneal injection after the induction of pancreatitis in the CS group. Rats in the SO group were subjected to a sham surgery that the pancreas and duodenum were flipped a number of times. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum activities of amylase (AMY), levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured by using a fully automatic chemistry analyzer. The head of pancreas and renal tissues were harvested and pathological change was observed under the light microscope. Expressions of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and Caspase-3 in renal tissues were evaluated by immunohistochemistry assay. Results ① Compared with the SO group, the damages of the pancreas and kidney tissues were significantly worse in the SAP group, and the above damages in the CS group were significantly decreased when comparing with the SAP group. ② Compared with the SO group, the serum activities of AMY, levels of BUN and Cr were significantly increased in the SAP group (P<0.05). The serum activities of AMY, levels of BUN and Cr in the CS group were significantly lower than those of the SAP group (P<0.05). ③ Compared with the SO group, the integrated optical density (IOD) of NF-κB, TNF-α, ICAM-1, and Caspase-3 in renal tissues were significantly increased in the SAP group (P<0.05), and the above indicators in kidney tissues of the CS group were significantly decreased when comparing with the SAP group (P<0.05). Conclusions CS can mitigate severe acute pancreatitis-induced renal injuries in rats, it ameliorates renal injury and improves renal function. The mechanism for the above improvements is that CS can widely inhibit the activation of NF-κB, and then downregulate the expressions of TNF-α, ICAM-1, and Caspase-3.
ObjectiveTo determine the effectiveness of Yidantong recipe retained enema combined with external application of Jinhuang powder on non-severe acute pancreatitis (NSAP). MethodsA total of 134 patients with NSAP, admitted to the Third People’s Hospital of Chengdu from September 2019 to August 2022 were included in this retrospective cohort study. All patients received routine Western medicine treatment, and they were divided into a observation group (n=66) and a control group (n=68) based on whether they underwent treatment of Yidantong recipe retained enema combined with external application of Jinhuang powder. The variables including incidence of adverse clinical outcome events, severity scores after treatment, the recovery time of flatus and bowel movement, duration of fasting food and water, scores of traditional Chinese medicine (TCM) syndromes and numerical value of blood indices before and after treatment, and the treatment effect of the two groups were statistically analyzed. ResultsCompared with that of the control group, the incidence of multiple organ dysfunction syndrome (MODS) and severe acute pancreatitis (SAP) of the observation group was lower (P<0.05), and the reduction before and after treatment of APACHEⅡ score, BISAP score and Ranson score in the observation group was more than those in the control group (P<0.05). Compared with that of the control group, the recovery time of flatus and bowel movement and duration of fasting food and water of the observation group was shorter (P<0.05). The reduction before and after treatment of the scores of TCM syndromes (abdominal pain, abdominal distention, nausea and vomiting, dry mouth and bitter taste) and numerical value of blood amylase (AMY), alanine aminotransferase (ALT), alanine aminotransferase (AST) and C-reactive protein (CRP) in the observation group were more than those in the control group (P<0.05). Compared with that of the control group (83.33%), the total effective rate of the scores of TCM syndromes (95.59%) of the observation group was higher (P<0.05).ConclusionYidantong recipe retained enema combined with external application of Jinhuang powder in the treatment of NSAP is effective by combining with routine Western medicine.
ObjectiveTo summarize the blood routine indexes and predictive systems that can predict the severity of acute pancreatitis (AP). MethodThe recent domestic and foreign literatures on the predictive value of blood routine indexes for the severity of AP were reviewed.ResultsFrom the current research results at domestic and foreign, independent blood routine indexes such as red blood cell distribution width, average platelet volume, hematocrit (TCT), platelet (PLT) count, platelet distribution width, percentage of immature granulocytes (IG%), and some blood routine calculation indexes such as neutrophil to lymphocyte ratio (NLR), PLT to lymphocyte ratio (PLR), red blood cell distribution width to PLT ratio (RPR), neutrophil-monocyte product, and so on, all had different predictive value for the severity of AP. In addition, multiple prediction modes such as blood routine indexes combined with some serological indexes or other scoring systems could also be used to predict the severity of AP. In general, the predictive value of the NLR, IG%, and HCT on the severity of AP had been unanimously recognized by researchers. However, the conclusions of related studies on the predictive values of PLT, PLR, and RPR on the severity of AP were still controversial. ConclusionsAt present, there are a variety of blood routine indexes can be used to predict severity of AP, but their predictive values are different. Further researches are still needed.
Objective To investigate the protective effect of 4-phenylbutyric acid (PBA) on liver injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group,n=8), SAP group (n=8), and PBA group (n=8). SAP model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in SAP group and PBA group. PBA solution (50 mg/kg) was administeredvia intraperitoneal injection for 3 days prior to establishing models in PBA group. Rats were injected equivalent saline solution instead of PBA solution in SAP group and SO group. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were measured using a fully automatic chemistry analyzer. The head of pancreas and right lobe of hepatic tissues were harvested and pathological examination was observed under the light microscope. Expressions of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and Caspase-3 in hepatic tissues were evaluated by immunohistochemistry assay. Results Compared with SO group, the serum levels of AMY, ALT and AST were significantly increased in SAP group (P＜0.05). The serum levels of ALT and AST in PBA group were significantly lower than those in SAP group (P＜0.05). There was no difference of the serum levels of AMY between in PBA group and SAP group (P＞0.05). Compared with SO group, the damages of the pancreas and liver tissues and the expressions of GRP78, CHOP and Caspase-3 in hepatic tissues were significantly increased in SAP group (P＜0.05). And the above indices in PBA group were significantly decreased when compared with SAP group. Conclusions PBA can alleviate severe acute pancreatitis-induced liver injury, and the mechanism may be associated with inhibition of endoplasmic reticulum stress (ERS) and reduction of hepatocyte apoptosis.