AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,s...AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.展开更多
AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis an...AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L�展开更多
AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) a...AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.展开更多
基金Supported by Medical University of Gda■sk,grant W-120,Poland
文摘AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.
文摘AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L�
文摘AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.
