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首页> 外文期刊>American Journal of Physiology >Dysregulation of the calpain-calpastatin system plays a role in the development of cerulein-induced acute pancreatitis in the rat.
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Dysregulation of the calpain-calpastatin system plays a role in the development of cerulein-induced acute pancreatitis in the rat.

机译：钙蛋白酶-钙帕他汀系统的失调在大鼠由小脑素诱发的急性胰腺炎的发展中起作用。

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Calpain, a calcium-dependent cytosolic cysteine protease, is implicated in a multitude of cellular functions but also plays a role in cell death. Recently, we have shown that two ubiquitous isoforms, termed micro-calpain and m-calpain, are expressed in rat pancreatic acinar cells and that calcium ionophore-induced calpain activation leads to acinar cell injury. On the basis of these observations, we have now investigated the role of both calpain forms and the endogenous calpain inhibitor calpastatin in acute pancreatitis. After treatment of rats either without or with calpain inhibitor Z-Val-Phe methyl ester (ZVP; 60 mg/kg i.p.), pancreatitis was induced by cerulein injections (10 microg/kg i.p.; 5 times at hourly intervals). Calpain activation and calpastatin expression in the pancreatic tissue were studied by Western blot analysis. Pancreatic injury was assessed by plasma amylase activity, pancreatic wet/dry weight ratio (edema), histological and electron-microscopic analyses, as well as fluorescencelabeling of actin filaments. Cerulein caused an activation of both micro-calpain and m-calpain, accompanied by degradation of calpastatin. Prophylactic administration of ZVP reduced the cerulein-induced calpain activation but had no effect on calpastatin alterations. In correlation to the diminished calpain activity, the severity of pancreatitis decreased as indicated by a decline in amylase activity (P < 0.01), pancreatic edema formation (P < 0.05), histological score for eight parameters (P < 0.01), and actin filament alterations. Our findings support the hypothesis that dysregulation of the calpain-calpastatin system may play a role in the onset of acute pancreatitis.
机译：钙蛋白酶是一种钙依赖性的胞质半胱氨酸蛋白酶，与多种细胞功能有关，但在细胞死亡中也起作用。最近，我们已经表明，在大鼠胰腺腺泡细胞中表达了两种普遍存在的亚型，分别称为微钙蛋白酶和间钙钙蛋白，钙离子载体诱导的钙蛋白酶活化会导致腺泡细胞损伤。基于这些观察，我们现在研究了钙蛋白酶形式和内源钙蛋白酶抑制剂钙蛋白酶他汀在急性胰腺炎中的作用。用或不用钙蛋白酶抑制剂Z-Val-Phe甲酯（ZVP; 60 mg / kg腹腔注射）治疗大鼠后，通过注射铜蓝蛋白（10 microg / kg i.p .;每小时间隔5次）诱发胰腺炎。通过蛋白质印迹分析研究了胰腺组织中钙蛋白酶的活化和钙蛋白酶抑素的表达。通过血浆淀粉酶活性，胰腺干/湿重比（水肿），组织学和电子显微镜分析以及肌动蛋白丝的荧光标记来评估胰腺损伤。 Cerulein引起了微钙蛋白酶和间钙蛋白酶的激活，并伴有钙蛋白酶抑制素的降解。 ZVP的预防性给药减少了青霉素诱导的钙蛋白酶激活，但对钙蛋白酶抑制素的改变没有影响。与钙蛋白酶活性降低相关，胰腺炎的严重程度降低，表现为淀粉酶活性下降（P <0.01），胰腺水肿形成（P <0.05），八个参数的组织学评分（P <0.01）和肌动蛋白丝变更。我们的发现支持以下假设，即钙蛋白酶-钙蛋白酶抑制系统的失调可能在急性胰腺炎的发作中起作用。

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