AIM： To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis. METHODS： Nice had cerulein administration to induce a...AIM： To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis. METHODS： Nice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride （GdCh） to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. Myeloperoxidases （MPO） assessed neutrophil infiltration. Interleukin-6 （IL-6） and IL-10 were measured in serum, pancreas, lungs and liver. RESULTS： In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCh had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects. CONCLUSION： Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.展开更多
AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. H...AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase （AMY） and pancreatic acinar cell apoptosis. The level of protein kinase C （PKC） membrane translocation in pancreatic tissue was detected by Western blot.RESULTS： In the hyperlipidemia model established by Triton WR1339, triglyceride （TG） increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals （P 〈 0.05） and decreased after albumin therapy but not significantly （P 〉 0.05）. Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy （P 〈 0.05）.CONCLUSION： Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.展开更多
AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induce...AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis (AEP).METHODS: Fifty Wistar rats were randomly divided into control group (n=10) and AEP group (n=40). A model of AEP was established by subcutaneous injection of cerulein 5.5 and 7.5 μg/kg at 0 and 1 h after the beginning of experiment respectively. PECAM-1 expression on PMNs from splenic vein and inferior vena cava was determined by RT-PCR at mRNA level and determined by flow cytometry at protein level.RESULTS: In experimental rats, an increased PECAM-1mRNA expression was seen from 4 to 8 h of AEP in peripheral circulation (0.77±0.25%, 0.76±0.28%, 0.89±0.30%,1.00±0.21% ), while in pancreatic microcirculation,expression decreased from 2 h and reached the lowest level at 6 h of AEP (0.78±0.29%, 0.75±0.26%, 0.62±0.28%,0.66±0.20%). There were significant differences at 8-h time point of AEP between peripheral circulation and pancreatic microcirculation (1.00±0.21% vs0.66±0.20%, P＜0.05).Meanwhile,the difference at protein level was also found.CONCLUSION: A reverse expression of PECAM-1 on PMNs was found between peripheral circulation and pancreatic microcirculation, suggesting that inhibition of PECAM-1expression may improve the pathological change of AEP.展开更多
基金Supported by a grant from the Fonds National Suisse de la Recherche Scientifique N°3200B0-100764 to Jean-Louis Frossard
文摘AIM： To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis. METHODS： Nice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride （GdCh） to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. Myeloperoxidases （MPO） assessed neutrophil infiltration. Interleukin-6 （IL-6） and IL-10 were measured in serum, pancreas, lungs and liver. RESULTS： In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCh had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects. CONCLUSION： Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.
基金Supported by the Key Program of Beijing Academy of Health, No. 1998-11-2001-09
文摘AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase （AMY） and pancreatic acinar cell apoptosis. The level of protein kinase C （PKC） membrane translocation in pancreatic tissue was detected by Western blot.RESULTS： In the hyperlipidemia model established by Triton WR1339, triglyceride （TG） increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals （P 〈 0.05） and decreased after albumin therapy but not significantly （P 〉 0.05）. Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy （P 〈 0.05）.CONCLUSION： Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.
基金Supported by National Natural Science Foundation of China, No.39925032
文摘AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis (AEP).METHODS: Fifty Wistar rats were randomly divided into control group (n=10) and AEP group (n=40). A model of AEP was established by subcutaneous injection of cerulein 5.5 and 7.5 μg/kg at 0 and 1 h after the beginning of experiment respectively. PECAM-1 expression on PMNs from splenic vein and inferior vena cava was determined by RT-PCR at mRNA level and determined by flow cytometry at protein level.RESULTS: In experimental rats, an increased PECAM-1mRNA expression was seen from 4 to 8 h of AEP in peripheral circulation (0.77±0.25%, 0.76±0.28%, 0.89±0.30%,1.00±0.21% ), while in pancreatic microcirculation,expression decreased from 2 h and reached the lowest level at 6 h of AEP (0.78±0.29%, 0.75±0.26%, 0.62±0.28%,0.66±0.20%). There were significant differences at 8-h time point of AEP between peripheral circulation and pancreatic microcirculation (1.00±0.21% vs0.66±0.20%, P＜0.05).Meanwhile,the difference at protein level was also found.CONCLUSION: A reverse expression of PECAM-1 on PMNs was found between peripheral circulation and pancreatic microcirculation, suggesting that inhibition of PECAM-1expression may improve the pathological change of AEP.
