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AIM:Using Toll-like receptor 4 gene knockout (tlr4-/-) mice and the wild-type (WT) mice with the same C57BL/10J genetic background, the effects of HU210, a cannabis preparation, on caerulein (CAE)-induced acute pancreatitis (AP) and the potential mechanisms were investigated.METHODS:WT or tlr4-/-mice were randomly divided into AP group, AP+HU210 group and control group.AP was induced by intraperitoneal injection of CAE (50 μg·kg-1·h-1) for a total of 6 times and lipopolysaccharide (LPS) at 10 mg/kg 6 h after the first injection of CAE.HU210 (50 μg/kg) was given 30 min before and 4 h after the first injection of CAE in AP+HU210 group.The animals in control group were given normal saline instead of CAE and LPS in the same way.The mice were sacrificed 3 h after the last injection.The blood, the pancreas, the lungs and the intestinal Peyer's patches were harvested.RESULTS:Compared with control group, the pancreatic pathological score and P38 protein expression, plasma amylase activity and inflammatory mediator levels, and lung MPO activity were significant increased (P<0.05) in both WT and tlr4-/-mice with AP.Compared with the WT mice with AP, the tlr4-/-mice with AP showed significantly low levels of IL-6, TNF-α and MCP-1 in the plasma, low expression levels of pancreatic P38 and p-P38 protein (P<0.05), and mild alterations of CD3+ T-lymphocytes, CD4+ T-lymphocytes and the ratio of CD4+/CD8+ (P<0.05).The administration of HU210 attenuated the pancreatic pathological changes and the lung MPO activity in both stains of mice with AP (P<0.05).However, the inhi-bitory effects of HU210 on the increased amylase activity in the plasma and the increased protein levels of pancreatic P38 and p-P38 were remarkable (P<0.05) in WT mice instead of in tlr4-/-mice.CONCLUSION:TLR4 is mainly involved in AP-related systemic inflammatory response and its mechanism may be dependent on TLR4-P38 MAPK signaling pathway.The intervention of HU210 in AP plays a protective role mainly by inhibiting the infiltration of inflammatory cells, and the relationship with TLR4 signaling pathway is not obvious.
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[ ABSTRACT ] AIM: To investigate the protect effect of Chinese herbal preparation, Qing Yi TangⅡgranule (QYT), on acute pancreatitis (AP) mice and its mechanism.METHODS:Adult male and female C57BL/6 mice (n=24) were randomly divided into control group, AP group and AP+QYT group.Severe AP was induced by combined intra-peritoneal injection of caerulein (50μg/kg) and lipopolysaccharide (LPS;10 mg/kg).Drinking water or 24%QYT solu-tion was given to the mice in AP group or AP+QYT group by oral gavage.The mice in control group were intraperitoneally injected with equivalent volume of normal saline and gavaged with water.The mice were sacrificed 3 h after the last injec-tion.Severity of AP was assessed by biochemical markers and histology.The plasma level of IL-6 and MCP-1, and lung myeloperoxidase ( MPO) levels were determined for assessing the extent of systemic inflammatory response.The intestinal microflora, T lymphocytes and T-lymphocyte subgroups were examined for assessing the function of the intestinal barrier. RESULTS:Compared with control group, the mice in AP group presented significant increases in pathological histological scores, plasma amylase activity and IL-6 and MCP-1 levels, as well as the MPO activity in the lung and pancreatic tissues. QYT attenuated these changes to some extent.Furthermore, the increased intestinal microflora was significantly reversed by QYT.No difference of the numbers of Peyer’ s patches in small intestine in the 3 groups was observed, but the percentage of CD3 +T lymphocytes decreased significantly in AP group, and increased percentage of CD4 +and CD4 +/CD8 +ratio were found in AP group and AP+QYT group.CONCLUSION: QYT protects against cearulein and LPS-induced acute pancreatitis in mice.The mechanisms may be related to the suppression of the inflammatory response, promoting intestinal bacteria removal, and regulating the functions of T lymphocytes in the intestinal barrier.
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AIM:We conducted an evaluation of clinical data with meta analysis to investigate the preventive effect of 5-aminosalicylic acid (5-ASA) on inflammatory bowel disease ( IBD)-associated colorectal cancer ( CRC) or dys-plasia (Dys) (IBD-CRC/Dys).METHODS: The information was retrieved from the main databases such as PubMed, Web of Science, the Cochrane Library, etc.All full-text articles about the prevention of IBD-CRC/Dys by 5-ASA were in-cluded if they conformed to the standards.The odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. According to the types of IBD and the treatment course, the subgroup analysis was conducted, respectively.RESULTS:Fifteen articles were selected, including 5 038 IBD patients.Pooled analysis showed a protective association between 5-ASA and IBD-CRC/Dys (OR=0.53, 95%CI:0.37~0.76).Among them, both ulcerative colitis patients (OR=0.45, 95%CI:0.27~0.77) and Crohn disease patients ( OR=0.39, 95% CI:0.16~0.97) with 5-ASA therapy were less likely to develop CRC/Dys compared with those without 5-ASA treatment.5-ASA treatment for 1~20 years shows a pre-ventive benefit (OR=0.43, 95%CI:0.25~0.74).However, a minimum 5-ASA exposure of 2~6 months did not show a preventive benefit (OR=0.59, 95%CI:0.26~1.34).CONCLUSION:5-ASA protects against CRC/Dys in IBD pa-tients.Additionally, the protective effect is treatment time dependent.Treatment course for 1~20 years shows an evident preventive benefit.
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Endocannabinoid system has several kinds of receptors, all of which have correspondence ligands and pathways of synthesis and degradation, and they belong to G-protein coupled receptors family. Recently studies show that stimulation of cannabinoid receptors has inhibitory effects on gastrointestinal motility and secretion. In this article, we introduce the compositions of the cannabinoid family members, includingtheir receptors, ligands, and antagonists, and their effects on the gastrointestinal motility and secretion. Useful information can be provided for the further study on the effects of endocannabinoid system on gastrointestinal motility and secretion, providing theoretic evidences for clinical use of cannabinoid.
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Cholangiocytes are the epithelial cells that line the intrahepatic biliary tree and also the target of cholangiopathies. Despite the heterogeneous etiology ,most of cholangiopathies share the common pathological process which is the imbalance between proliferation and apoptosis of cholangiocytes. The article is a review about the characteristics and mechanism of proliferation and apoptosis of cholangiocytes and their relationship to cholangiopathies.
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Postoperative ileus is commonly referred to the inhibition of gastrointestinal motility after ab-dominal surgery. Some causes are responsible for the ileus, including postoperative pain and electrolyte im-balances, and manipulations during surgery. Although gastrointestinal motility normalizes spontaneously in most patients, some develop severe to postoperative ileus, which is difficult to treat, with a delayed recovery from surgery, prolonged hospital stay, and increased treatment costs. So, it is essential to understand the mechanisms of postoperative ileus for effective prevention and treatment.
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Acute pancreatitis is one of the common clinical diseases in emergency.The severe acute pancreatitis-associated ascetic fluid is always found in clinic.Its roles related multiple organ dysfunction(MOD)in acute pancreatitis is being understood.In this article，the possible compositions of the ascites，the mechanism of its formation，and its effect on body are recited，in order to better understand the mechanism，the prevention and the treatment of the acute pancreatitis and its compications related MOD.
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Cannabinoids have been used in clinic for many years.However,their effective mechanisms,especially the role of the endogenous cannabinoid system in the regulation of intestinal motility are still poorly understood.In this article,we introduced that the compositions of the Cannabinoid family members,including their receptors,analogues,and antagonists,and the effects of them on the gastrointestinal movement.We provide the useful update information for the further clinic and experiment study on the cannabinoid family and the endocannabinoid system.
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<p><b>OBJECTIVE</b>To investigate the effect of Ca(2+) on lipopolysaccharide (LPS)-induced NF-kappa B activation in pancreatic acinar cells and the role of NF-kappa B in LPS-induced acinar cell injury.</p><p><b>METHODS</b>Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to varying concentrations of LPS (from 1 to 20 mg/L) in the presence or absence of EGTA. At various time points (30 minutes, 1 hour, 2 hours, 4 hours and 10 hours) after treatment with the agents, cell viability was determined by MTT. Nuclear translocation of NF-kappa B's subunit p65 was visualized by immunofluorescence staining and nuclei protein was extracted to perform EMSA which was used to assay the activity of NF-kappa B binding to the DNA sequence containing the recognition site of NF-kappa B.</p><p><b>RESULTS</b>LPS induced cell damage in a time- and concentration-dependent manner while EGTA attenuated LPS-induced cell damage (P < 0.05). NF-kappa B p65 immunofluorescence staining had increased intensity in the cytoplasm and indicated that nuclear translocation occurred within 30 minutes and its zenith was reached at 1 hour after LPS (10 mg/L) treatment. Testing of NF-kappa B DNA binding activity showed the same alteration phase as p65 immunofluorescence staining. NF-kappa B activation preceded the pathological alteration of pancreatic acinar cells. The Ca(2+) chelator EGTA inhibited LPS-induced NF-kappa B activation.</p><p><b>CONCLUSIONS</b>NF-kappa B activation is an important early event in LPS-induced injury to pancreatic acinar cells. Ca(2+) is an important mediator in the process of LPS-induced NF-kappa B activation.</p>
Subject(s)
Animals , Male , Rats , Calcium , Pharmacology , Lipopolysaccharides , Pharmacology , NF-kappa B , Physiology , Pancreas , Cell Biology , Rats, Sprague-DawleyABSTRACT
AIM: To investigate the alteration of classical protein kinase C-?(cPKC-?)in the ascitic white blood cells of rats with acute pancreatitis (AP), and explore the effects of aspirin (ASP) or tetrandrine (Tet) on them. METHODS: The total of 56 health SD rats were divided into four groups, AP+ASP group, AP+Tet group, AP+normal saline (NS) group, and sham operation control (SO) group. AP model was induced by a retrograde injection of 3% sodium deoxycholate into the pancreatic duct. The AP+Tet group received a intraperitoneal injection of Tet (80 (mg/kg)), respectively. The AP+ASP group received an infusion of ASP (12.5 mg/100 g) by use of a nose-gastric catheter. At 1 h, 5 h after the treatment, cPKC-? in the ascitic white blood cells of AP rats was measured by Western blot and chemiluminescence, and the semi-quantitative values was obtained by Gel-pro analyzer. RESULTS: The values of cPKC-? decreased in AP+NS group, but increased significantly in the groups treated with ASP and Tet (P
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Although we have understood only limited knowledge about the pathophysiological mechanisms of acute pancreatitis (AP),it has at least been proven that the activation of pancreatic zymogens inside the pancreatic acinar cells,as well as the inflammatory reaction resulting from the inflammatory mediators,including the cytokines and oxygen free radicals,constitute the main reason for the early pathological processes of AP. The inflammatory mediators also facilitate the complications such as lung injury and multiple organ dysfunctions. The bacterial translocation,which aggravates the pathological changes and increases the mortality in AP,causes the pathophysiological vicious circle in the later period of the disease. There is no doubt that the levels of the clinical prevention,diagnosis and treatment for AP will be greatly improved along with the elucidation of its pathogenesis.
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AIM: To investigate the change of Cpn60 content,the alterations of pancreatic enzymes and lysosome,in order to better understand the mechanism of intrapancreatic enzyme activation in acute pancreatitis(AP). METHODS: The AP model was replicated by retrograde infusion of 4% sodium-deoxycholate in the choledocus of SD rats. The levels of amylase in plasma and TNF-? in pancreatic tissue were measured by biochemical technique at 5 h and 10 h after AP induction. The content of Cpn60 and pancreatic enzymes in different compartments of the acinar cells were tested by quantitative protein A-gold immunocytochemistry technique. The change of lysosome in the acinar cells was observed under the electronic microscope. RESULTS: After AP was induced,the levels of amylase in the plasma and TNF-? in the pancreatic tissue increased significantly. Lysosomes with different forms were found inside the acinar cells,and some of them located in the Golgi apparatus. Cpn60 content decreased,which was accompanied by an increase of lipase or chymotrypsinogen content in the pancreatic secretory pathway. CONCLUSION: In the pancreatic acinar cells of AP rats,Cpn60 content decreased,suggesting an insufficient chaperone capacity,and combining with the change of lysosome both in its amount and location,which may take part in the intrapancreatic enzyme activation and the development of AP.
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Acute necro-hemorrhagic pancreatitis (ANHP) was induced in rats by intra-pancreatic duct injection with a mixed solution of bile salt and trypsin. After 6- to 30-hr of operation the increase of plasma lipidperoxidant (LPO) levels from 4.67 to 20.5 nmol/ml and the fall of plasma amylase levels from 6577 to 2629 U were observed in the rats with ANHP. The values of the plasma LPO at 10-,20-,and 30-hr in the rats with ANHP were significantly higher than those in the control (P