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.
ObjectiveTo summarize the clinical application of the minimally invasive step-up approach in the treatment of severe acute pancreatitis (SAP), and to explore the clinical indications, timing for the minimally invasive step-up approach, and to make comparison with open necrosectomy.
MethodsThe literatures about the treatment of SAP in recent years were collected to make a review.
ResultsThe minimally invasive step-up approach, comparing with open necrosectomy, was more effective to treat SAP, however, itself had its own limitations. In the treatment process, the optimal method was minimally invasive step-up approach, but also did not exclude open necrosectomy.
ConclusionsThe treatment of SAP can not rely on a single method, it needs a comprehensive treatment which is relate with multidisciplinary management and highly individual choice. In addition, it needs further study to explore the timing and indications for transforming minimally invasive step-up approach into open necrosectomy.
ObjectiveTo evaluate the clinical efficacy of surgical intervention combined with endoscopic ultrasound-guided transluminal drainage in the treatment of infected pancreatic necrosis (IPN). MethodsA retrospective, historical control study was conducted. A total of 98 patients with acute pancreatitis (AP) complicated with IPN who met the inclusion and exclusion criteria and were admitted to the Third People’s Hospital of Chengdu from June 2016 to January 2023 were selected as the research objects. The endoscopic ultrasound-guided transluminal drainage was carried out in our hospital in June 2020. In this study, patients treated before May 2020 were divided into the non-EUS group (52 cases), and patients treated after June 2020 were divided into the EUS group (46 cases). The baseline data, surgical intervention, length of hospital stay, length of intensive care unit (ICU) stay, infection time, incidence of multiple organ dysfunction syndrome (MODS), survival situation, short-term and long-term complications, and other indicators were compared between the two groups. ResultsThe number of percutaneous catheter drainage (PCD, 1.0 vs. 1.0), the number of PCD drainage tube (1.0 vs. 2.0), the number of retroperitoneal debridement drainage (1.0 vs. 2.0), the total length of hospital stay (42.0 d vs. 45.5 d), the length of ICU stay (11.0 d vs. 14.0 d), the length of infection time (10.5 d vs. 18.5 d), the incidences of MODS [43.5% (20/46) vs. 67.3% (35/52)] and residual infection [28.3% (13/46) vs.48.1% (25/52)] in the EUS group were shorter (or lower) than those in the non-EUS group (P<0.05); but there were no significant differences in the number of endoscopic pancreatic stent implantation, the number of laparotomy, the number of laparoscopic surgery, and the incidences of abdominal bleeding, gastrointestinal fistula, gastrointestinal obstruction, chronic pancreatic fistula, chronic pancreatitis and incisional hernia between the two groups (P>0.05). ConclusionFor patients with AP complicated with IPN, surgical intervention combined with endoscopic ultrasound-guided transluminal drainage can reduce the number of PCD and drainage tube, shorten the total length of hospital stay, the length of ICU stay and infection, as well as reduce the incidences of MODS and residual infection.
Background Acute pancreatitis is one of the most severe acute abdominal conditions. Recently with the understanding of pathophysiology and pathogenesis of acute pancreatitis, cytokines, especially platelet-activating factor (PAF), have been shown to play an important role. Lexipafant is a potent inhibitor of PAF. It has shown exiting results in the animal experiments, so randomized controlled studies are needed to assess the impact of lexipafant for acute pancreatitis. Objectives To determine whether lexipafant can alter the course, prevent or treat organ failure and reduce mortality in acute pancreatitis. Search strategy Electronic databases were searched and reference lists from included studies were also handsearched. Published abstracts from conference proceedings and ten kinds of Chinese medical journals were handsearched for additional citations. Personal contaction with colleagues and experts in the field of pancreatitis was performed to identify potentially relevant trials. Selection criteria Randomized, controlled trials, In which participants went in hospital within 72 hours of belliache episode, comparing lexipafant to placebo or other interventions on organ failure rate or mortality of acute pancreatitis. Data collection and analysis Data related to the clinical outcomes were extracted by two reviewers independently, if there was any divarication, they would have a discussion. Main Results Three studies meet the inclusion criteria up to 2001. Compared with control group, lexipafant had the tendency of reducing the early deaths (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.23 to1.38, P=0.2), accelerating the recovery of organ failure (OR 0.40, 95%CI 0.12 to 1.32, P=0.13) and reducing the occurrence of new organ failure OR 0.34, but these results had no statistical significance. A large-scale multicentre randomized controlled trial including 1 500 patients has been completed in America, but the result has not been published. Reviewers’ Conclusions Current evidence couldn’t draw the final conclusion. So the large-scale of randomized controlled trials is required.
【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.
ObjectiveTo summary the effect of parenteral nutrition combined with enteral nutrition on patients with severe acute pancreatitis.
MethodsThe clinical data of 200 patients with severe acute pancreatitis admitted in our hospital in recent 10 years were retrospectively analyzed. Of which 88 cases were treated by traditional nutritional support therapy (traditional nutrition group), the rest of 112 cases of patients with early parenteral nutrition to later period gradually combined with enteral nutrition comprehensive nutritional support strategy (comprehensive nutrition group).
ResultsThe APACHEⅡscores and serum level of C-reactive protein (CRP) of patients in comprehensive nutrition group were significantly lower than patients in traditional nutrition group (P < 0.05), while the serum albumin level was significantly higher than that of traditional nutrition group (P < 0.05). In the incidence of complications and mortality, the average length of stay and total cost of comprehensive nutrition group were significantly lower than patients with traditional nutrition group (P < 0.05), the cure rate was significantly higher than that of traditional nutrition group (P < 0.05).
ConclusionThe combination of parenteral nutrition and enteral nutrition of nutrition support model not only can shorten the duration of symptoms but also alleviate the burden of patients and reduce complications and mortality.
Objective
To verify tissue factor (TF)-bearing microparticle (TF-MP) could be released from Kupffer cells (KCs) stimulated by lipopolysaccharide (LPS) and TF controlled by Toll-like receptor 4 (TLR4) could induce acute pancreatitis.
Methods
After the acute pancreatitis model completed, the wild type C57/BL6 mouse (WT group) and the TLR4-/- mouse (TLR4-/- group) received intraperitioneal injections of 10 mg/kg LPS. The degree of pathological lesion and the TF expression were detected in the pancreas tissue. The TF and TLR4 protein and mRNA expressions in the KCs were detected at 6, 12, and 24 h after the last injection of LPS. The survival rates were campared in these estabilshed acute pancreatitis model mice. The TF and TLR4 protein and mRNA expressions in the KCs stimulated with LPS (300 μg/L) were also detected at 0, 15, 30, 60, and 120 min. The TF and TF-MP levels were detected in the supernatants of the KCs at these time point.
Results
The injury of the pancreas in the TLR4-/- group was slighter than that in the WT group. The TF proteins in the liver and pancreas tissues of the TLR4-/- group were significantly lower than those of the WT group (P<0.05). The survival rate of the TLR4-/- group was significantly higher than that of the WT group under the situation of the acute pancreatitis (P<0.05). The TLR4 and TF protien and mRNA expressions of the KCs were significantly decreased in the TLR4-/- group as compared with the WT group at 30, 60, and 120 min (P<0.05). The levels of TF and TF-MP in the supernatant of the TLR4-/- group were significantly lower than those of the WT group at 30, 60, and 120 min (P<0.05).
Conclusion
Acute pancretitis can be induced by TF and TF-MP expressions in KCs which could be regulated by TLR4 pathway.
ObjectiveTo understand the current progress of programmed cell death in the pathogenesis of acute pancreatitis, and to provide reference for the pathogenesis and treatment of acute pancreatitis.MethodThe research progress of acute pancreatitis and programmed cell death in recent years was reviewed by reading relevant literatures at home and abroad in recent years.ResultsProgrammed cell death was defined as controlled cell death performed by intracellular procedures, including apoptosis, autophagy, programmed necrosis, and coronation. The pattern of death of pancreatic acinar cells mainly includes apoptosis and programmed necrosis. Although the pathogenesis of acute pancreatitis had not yet been fully clarified, it was known that through the study of programmed cell death, it could help us to understand the pathogenesis and pathogenesis of acute pancreatitis and provide more effective treatment methods.ConclusionsProgrammed cell death is very important for acute pancreatitis. The mechanism of programmed cell death in acute pancreatitis is necessary for the treatment and prevention of it.
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.
ObjectiveTo summarize progress of immune response in severe acute pancreatitis (SAP) and to provide a basis for appropriate immunotheraphy.MethodThe relevant literatures about the effect of immune response in the SAP with infectious complications in recent years were reviewed.ResultsThe inflammatory cascade reaction occurred in the early stage of SAP. Subsequently, the compensatory anti-inflammatory response syndrome (CARS) arised and immune response of the organism was suppressed. At this stage, the rate of infection was higher than before.ConclusionsCARS is one of major reasons in SAP with infectious complications. At present, fluid infusion, fasting, parenteral nutrition and like are major therapies in SAP. If corresponding immunotherapy could be carried out according to immune mechanism of SAP infection, that is, early appropriate immunosuppressive therapy and dynamic monitoring of body’s immune system state should be performed, when it is found that immunosuppression is present, appropriate immunostimulus therapy will be possible to reduce mortality of SAP and improve its prognosis.
