硫酸软骨素对ANP大鼠胰腺细胞氧化应激损伤及细胞间连接的影响

目的:探讨硫酸软骨素（CS）预处理对大鼠急性坏死性胰腺炎（ANP）及其组织氧化应激损伤的影响。方法：雄性Wistar大鼠90只随机分3组：A组为ANP组;B组为CS组;C组为假手术组。3组动物于术后30min，1h，3h，6h，12h分批处死。检测血清淀粉酶（SAM）、计算胰腺系数、胰腺组织中MDA、GSH、SOD和ATP含量。透射电镜观察细胞间连接的变化。在激光共聚焦显微镜下观察E-cadherin在细胞内分布、定位的变化。Western-blot进行E-cadherin蛋白半定量检测。结果：A，B组SAM水平升高，但B组明显低于A组。A组胰腺组织中GSH，SOD，ATP明显下降（P<0.01），MDA明显升高(P<0.01)。B组GSH，SOD，ATP下降幅度较小，MDA升高幅度小，与A组差异均有显著性（均P<0.05）。A组胰腺系数迅速升高并持续增长（P<0.01）;细胞间连接损伤;E-cadherin弥漫分布于胞浆内，其蛋白含量持续下降（P<0.05），与B，C组比较，均有显著性差异。结论：在实验性ANP早期，胰腺组织中内源性抗氧化物质显著下降，脂质过氧化增加，能量耗竭，使细胞间连接复合体损伤从而引起胰腺水肿。CS可明显减轻ANP大鼠胰腺细胞氧化应激损伤及能量耗竭，缓解E-cadherin的降解，稳定细胞连接从而减轻胰腺水肿。

The effects of chondroitin-sulfate on cellular oxidation stress injury and on adhesion junction during experimental acute necrotizing pancreatitis

Abstract:Objective：To explore the effects of administration of chondritin-sulfate(CS) on acute necrotizing pancreatitis(ANP) and its associated tissue oxidation stress injury.Methods：Male Wistar rats(n=90) were divided randomly into three groups：group A, ANP group; group B, ANP rats received chondroitin-sulfate therapy; group C, control group．Rats in three groups were killed at 30min,1h,3h,6h,and 12h after operation, respectively．The levels of pancreatic indexes (pancreatic wet/body weight),malonyl dialdehyde (MAD)、total superoxide dismutase (SOD),glutathione (GSH)、ATP and serum amylase (SAM) were measured．Changes of adhesion junctions were examined by using a electron microscopy．The cellular distribution and changes of localizetion of E-cadherin was observed by confocal fluorescence microscopy; an adhesion junction protein expression was studied by western-blot method．Results：Compared with group B, Levels of GSH、SOD and ATP in group A decreased markely （P<0.01）,however MDA increased significantly (P<0.01).In group A，compared with B and C group, it demostrated a rapid and sustained increase in levels of pancreatic indexes(P<0.01); damages of adhesion junctions E-cadherin was localized at the cytoplasm, the level of E-cadherin protein was markedly decreased(P<0.01)．Conclusions：In the early stage of experimental ANP, in pancreat tissue, the CSH, SOD and ATP decredsed significantly,resulting in severe damage of adhesion junction，which was responsible for the formation of pancreatic edema．Treatment with CS can protect adhesion junction by increasing E-cadherin protein concentration, and thus relieve pancreatic edema．