OBJECTIVETo set up a convenient nontraumatic mouse model of severe acute pancreatitis(SAP).

METHODSMice received intraperitoneal injections with caerulein and lipopolysaccharide (LPS). Serum amylase and pancreatic moisture content were measured during experiment. The histo pathological changes of pancreas and relevant organs were observed under light microscope.

RESULTSSerum amylase and pancreatic moisture content increased and pancreatic interstitial edema, inflammatory cellular infiltration, parenchymal necrosis as well as parenchymal hemorrhages were happened in the caerulein plus LPS group, and the lesions of other organs including stomach, ileum, spleen, and lung were seen as well. In the careulein group, there was only pancreatic interstitial edema with no parenchmal necrosis or hemorrhage, and the rest organs were normal.

CONCLUSIONSThe SAP mouse model induced by caerulein plus LPS has the same pathological characteristics of human SAP, which can be used for human SAP studies.

Animals ; Ceruletide ; Disease Models, Animal ; Female ; Injections, Intraperitoneal ; Lipopolysaccharides ; Mice ; Pancreatitis, Acute Necrotizing ; chemically induced

Pancreatitis has not been reported in allogeneic stem cell transplant (allo-SCT) recipients with cyclosporine in China. This article presented a case of acute pancreatitis in a 49-year-old patient with AML-M2a who received allogeneic stem cell transplant from her HLA identical sister. The preparative regimen consisted of busulfan and cyclophosphamide. The cyclosporine A, short-term methotrexate and antilymphocyte globulin (ATG), were used to prevent the graft-versus-host disease (GVHD). Clinical and laboratory signs of acute pancreatitis were found in the patient on day 20 post-transplant. A diagnosis of acute pancreatitis was made although the pancreas was apparently normal at abdominal contrast-enhanced tomography and ultrasonography. She recovered with supportive care and reduction of cyclosporine dose. In conclusion, cyclosporine is the probable cause of pancreatitis in this patient.
Cyclosporine ; adverse effects ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Middle Aged ; Pancreatitis, Acute Necrotizing ; chemically induced ; Postoperative Complications ; chemically induced

A stable and reliable infected necrotizing pancreatitis (INP) model in rats was established in order to study the pathophysiological mechanism and pathological development rule of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium taurocholate in combination with different concentrations of E. coli (10(3), 10(4), 10(5)/mL, respectively) into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancreatic tissue. The results showed that acute necrotizing pancreatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. coli into the pancreatic duct and the positive rate of germ cultivation in group B was 0. The INP model was established in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h survival rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 10(4)/mL E. coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might be that the hemorrhage and necrosis of pancreatic tissue induced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs. Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.
Cholagogues and Choleretics/*pharmacology ; Disease Models, Animal ; Escherichia coli/*metabolism ; Injections, Intraperitoneal ; Pancreas/enzymology ; Pancreas/microbiology ; Pancreatic Ducts/enzymology ; Pancreatic Ducts/microbiology ; Pancreatitis, Acute Necrotizing/*chemically induced ; Pancreatitis, Acute Necrotizing/*microbiology ; Rats, Sprague-Dawley ; Taurocholic Acid/*pharmacology ; Time Factors

The role of PACAP (pituitary adenylate cyclase activating polypeptide), a peptidergic transmitter, in the pathogenesis of acute pancreatitis is not yet clear. This experiment was conducted to examine the action of exogenous PACAP on rat pancreas and on the course of experimental acute pancreatitis. The results showed that 5-30 microg/kg of PACAP slightly raised the serum amylase level, induced pancreatic edema (23.88% +/- 2.532%-25.86% +/- 1.974% of experiment groups versus 29.21% +/- 5.657% of control group), inflammatory cell infiltration, vacuolization of acinar cells, and occasionally fatty and parenchymal necroses. 15-30 microg/kg of PACAP aggravated cerulein-induced acute pancreatitis; the pancreatic edema became more marked (13.45% +/- 2.045%-17.66% +/- 4.652% of expreiment groups versus 21.83% +/- 3.013% of cerulein group, P<0.05), the serum amylase level became higher; and ascites, pancreatic bleeding, fatty and parenchymal necroses, and extensive vacuolization of acinar cells appeared. For sodium taurocholate-induced pancreatitis, 5-10 microg/kg of PACAP mildly attenuated the pancreatic edema, reduced the serum amylase level (1986.91 +/- 710.97-2944.33 +/- 1182.47 IU/L vs 3690.87 +/- 2277.99 IU/L, P<0.05), whereas it caused multifocal hemorrhage and prominent necrosis in pancreas. Except the cerulein-induced pancreatitis groups, other groups were found to have reduced pancreatic functional capillary density (FCD); when pancreatic edema was taken into consideration and calibrated FCD was introduced (FCD weighted against pancreatic wet/dry ratio), all groups revealed increases in pancreatic functional capillaries when compared with normal control. In conclusion, PACAP is proinflammatory in the pathogenesis of acute pancreatitis, PACAP plus cerulein can induce acute hemorrhagic/necrotizing pancreatitis, and the action of PACAP on cerulein-induced panceatitis may differ from that on sodium taurocholate-induced one. In this experiment, pancreatic FCD was underestimated due to pancreatic edema.
Amylases ; blood ; Animals ; Capillaries ; pathology ; Ceruletide ; Disease Models, Animal ; Male ; Pancreas ; blood supply ; Pancreatitis, Acute Necrotizing ; chemically induced ; enzymology ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of resveratrol on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis (SAP) and explore the mechanism of such effect.

METHODSD rats with 3.5% sodium taurocholate-induced SAP were treated with resveratrol, and the serum amylase was detected with automatic biochemistry analyzer. The apoptosis of the pancreatic acinar cells in the rats was detected by TUNEL assay, and the expression of Fas and FasL genes was determined by RT-PCR and Western blotting. The pathological changes of the pancreas were observed under optical microscope.

RESULTSCompared with SAP group, the resveratrol-treated rats showed obviously decreased serum amylase and scores for pancreatic histopathological lesions. Resveratrol treatment significantly increased the apoptotic indices of pancreatic acinar cells and the levels of FasL mRNA and protein in rats with SAP.

CONCLUSIONResveratrol produces important therapeutic effect on SAP in rats by inducing pancreatic acinar cell apoptosis possibly as a result of up-regulated FasL gene expression.

Animals ; Apoptosis ; drug effects ; Fas Ligand Protein ; drug effects ; genetics ; metabolism ; Male ; Pancreas, Exocrine ; pathology ; Pancreatitis, Acute Necrotizing ; chemically induced ; drug therapy ; pathology ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; therapeutic use ; Taurocholic Acid ; Up-Regulation

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.
Animals ; Antioxidants/*pharmacology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Male ; NF-kappa B/*drug effects/metabolism ; Pancreas/metabolism/pathology ; Pancreatitis, Acute Necrotizing/chemically induced/*drug therapy ; Pyrrolidines/*pharmacology ; RNA, Messenger/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates/*pharmacology ; Toll-Like Receptor 4/*drug effects/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.
Animals ; Antioxidants/*pharmacology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Male ; NF-kappa B/*drug effects/metabolism ; Pancreas/metabolism/pathology ; Pancreatitis, Acute Necrotizing/chemically induced/*drug therapy ; Pyrrolidines/*pharmacology ; RNA, Messenger/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates/*pharmacology ; Toll-Like Receptor 4/*drug effects/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism

OBJECTIVETo investigate the protective effect of resvertrol on the intestinal mucosal cells in rats with severe acute pancreatitis and explore the possible mechanism.

METHODSTwenty-four SD rats were randomly divided into the sham-operation (SO) group, severe acute pancreatitis (SAP) group and resveratrol-treated (RES) group. In the SO group, the pancreases were slightly flipped only. In the SAP and RES groups, SAP model was established by retrograde injection of 40 g/L sodium chrolate (1 ml/kg) through the pancreatic duct, and in the latter group, resveratrol (10 mg/kg) was given intravenously. Specimens were obtained 6 h after SAP model establishment and the endotoxin levels in the portal vein was determined with turbidimetry to evaluate the effect of resversatrol on the intestinal endotoxin translocation in SAP rats. Apoptosis of the mucosal cells was detected by TUNEL methods, and the expression of bax and bcl-2 mRNA were determined by RT-PCR. The mitochondrial membrane potential of the intestinal mucosal cells was measured by confocal microscopy.

RESULTSThe endotoxin levels in the portal vein were significantly lower in RES group than in SAP group (P<0.01). TUNEL assay demonstrated significantly higher apoptotic index of the mucosal cells in SAP group than that in RES group (P<0.01). The expression of Bax mRNA in the intestinal mucosal cell was significantly higher in SAP group than in RES group (P<0.01), whereas the expression of bcl-2 mRNA was significantly lower in SAP group (P<0.01). The mitochondrial membrane potential of the intestinal mucosal cell was significantly lower in SAP group than in RES group (P<0.01).

CONCLUSIONResvertrol can inhibit the apoptosis of the intestinal mucosa cells and maintain the integrity of the intestinal barrier to prevent the bacterial and endotoxin translocation in SAP.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; In Situ Nick-End Labeling ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Microscopy, Confocal ; Pancreatitis, Acute Necrotizing ; chemically induced ; drug therapy ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium Chloride ; Stilbenes ; pharmacology ; therapeutic use ; bcl-2-Associated X Protein ; genetics