Lee H S, Bhagat L, Frossard J L, Hietaranta A, Singh V P, Steer M L, Saluja A K
Department of Internal Medicine, Institute of Digestive Diseases and Nutrition, Korea University College of Medicine, Seoul, Korea.
Gastroenterology. 2000 Jul;119(1):220-9. doi: 10.1053/gast.2000.8551.
BACKGROUND & AIMS: Heat shock proteins (Hsps), induced by cell stress, are known to protect against cellular injury. Recent studies have indicated that Hsp60 expression, induced by exposure to water immersion stress, protects against pancreatitis induced by administration of supramaximal doses of cerulein in rats. However, the mechanisms responsible for this protection are not known.
Rats were water-immersed for 3-12 hours. Pancreatitis was induced by cerulein administration.
The results confirm that prior induction of Hsp60 expression by water-immersion stress significantly ameliorates the severity of cerulein-induced pancreatitis as judged by the markedly reduced degree of hyperamylasemia, pancreatic edema, and acinar cell necrosis. Water immersion also prevents the subcellular redistribution of cathepsin B from a lysosome-enriched fraction to a heavier, zymogen granule-enriched fraction that is known to occur in this model of pancreatitis. Intra-acinar cell activation of trypsinogen that occurs shortly after exposure to a supramaximally stimulating dose of cerulein both in vivo and in vitro is prevented by prior water-immersion stress and Hsp60 expression. The protection against pancreatitis that follows water-immersion stress is not caused by alterations of cholecystokinin receptors, because water immersion does not alter the typical biphasic amylase secretory response to stimulation with cerulein.
Water-immersion stress induces Hsp60 expression, ameliorates cerulein-induced pancreatitis, and prevents intra-acinar cell activation of trypsinogen. We suggest that Hsp60 protects against cerulein-induced pancreatitis by preventing trypsinogen activation within acinar cells.
热休克蛋白（Hsps）由细胞应激诱导产生，已知其可保护细胞免受损伤。最近的研究表明，暴露于水浸应激诱导的Hsp60表达可保护大鼠免受超最大剂量雨蛙素诱导的胰腺炎。然而，这种保护作用的机制尚不清楚。
将大鼠水浸3 - 12小时。通过给予雨蛙素诱导胰腺炎。
结果证实，水浸应激预先诱导Hsp60表达可显著减轻雨蛙素诱导的胰腺炎严重程度，这可通过高淀粉酶血症、胰腺水肿和腺泡细胞坏死程度明显降低来判断。水浸还可防止组织蛋白酶B在该胰腺炎模型中已知会发生的从富含溶酶体的部分向较重的、富含酶原颗粒的部分的亚细胞重新分布。在体内和体外，暴露于超最大刺激剂量雨蛙素后不久发生的腺泡细胞内胰蛋白酶原激活可被预先的水浸应激和Hsp60表达所阻止。水浸应激后对胰腺炎的保护作用不是由胆囊收缩素受体的改变引起的，因为水浸不会改变对雨蛙素刺激典型的双相淀粉酶分泌反应。
水浸应激诱导Hsp60表达，减轻雨蛙素诱导的胰腺炎，并防止腺泡细胞内胰蛋白酶原激活。我们认为Hsp60通过防止腺泡细胞内胰蛋白酶原激活来保护免受雨蛙素诱导的胰腺炎。
