Wagner A C, Metzler W, Höfken T, Weber H, Göke B
Department of Gastroenterology, University of Bern, Inselspital, Bern,
Digestion. 1999 Jan-Feb;60(1):41-7. doi: 10.1159/000007587.
The pathophysiology of pancreatitis and the pancreatic stress response are not well understood. In the pancreas, mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) are reportedly regulated by secretagogue stimulation and hyperstimulation. However, no data exist on the expression and regulation of pancreatic p38 Map kinase.
Pancreatic expression of p38 Map kinase and MAPK, SAPK and p38 regulation during pancreatic stress were investigated.
For hyperstimulation and secretory stress, cerulein was given intravenously, while hyperthermia preconditioning stress was induced by whole body hyperthermia (42 degreesC).
In addition to MAPK and SAPK, p38 Map kinase was found to be expressed in the rat pancreas. Cerulein regulated all kinases time- and dose-dependently. MAPK and p38 Map kinase showed basal activity and were further activated at low cerulein doses. SAPK had no basal activity and its activation required maximal secretory to supramaximal amounts of cerulein. Cerulein hyperstimulation, inducing pancreatitis, activated p38 more rapidly than SAPK and more strongly than MAPK. In contrast to cerulein hyperstimulation stress, hyperthermia stress only activated p38 Map kinase.
p38 Map kinase is expressed in the pancreas and is most rapidly activated following cerulein hyperstimulation. Both SAPK and p38 Map kinase are possibly important regulators during the onset of cerulein pancreatitis.
胰腺炎的病理生理学及胰腺应激反应尚未完全明确。据报道,在胰腺中,丝裂原活化蛋白激酶(MAPK)和应激激活蛋白激酶(SAPK)受促分泌剂刺激及过度刺激的调控。然而,关于胰腺p38丝裂原活化蛋白激酶的表达及调控尚无相关数据。
研究胰腺应激期间p38丝裂原活化蛋白激酶、MAPK、SAPK的胰腺表达及p38的调控情况。
为诱导过度刺激及分泌应激,静脉注射蛙皮素,而全身热疗(42℃)诱导热预处理应激。
除MAPK和SAPK外,还发现p38丝裂原活化蛋白激酶在大鼠胰腺中表达。蛙皮素对所有激酶的调控具有时间和剂量依赖性。MAPK和p38丝裂原活化蛋白激酶呈现基础活性,在低剂量蛙皮素作用下进一步激活。SAPK无基础活性,其激活需要最大分泌量至超最大量的蛙皮素。诱导胰腺炎的蛙皮素过度刺激比SAPK更快、比MAPK更强烈地激活p38。与蛙皮素过度刺激应激不同,热应激仅激活p38丝裂原活化蛋白激酶。
p38丝裂原活化蛋白激酶在胰腺中表达,在蛙皮素过度刺激后激活最快。SAPK和p38丝裂原活化蛋白激酶在蛙皮素性胰腺炎发病过程中可能均为重要调控因子。