Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany.
PLoS One. 2012;7(7):e39972. doi: 10.1371/journal.pone.0039972. Epub 2012 Jul 5.
Heat shock protein (Hsp) 72 is a molecular chaperone which is upregulated in response to a variety of stress situations and has a general cytoprotective function. Increased Hsp72 levels were implicated in protection from acute pancreatitis; a hypothesis which was not tested in a transgenic mouse model yet.
To analyze the role of Hsp72 during acute pancreatitis, well-characterized transgenic animals overexpressing rat Hsp72 (Hsp72 mice) under the control of the ß-actin promoter were subjected to caerulein- and L-arginine-induced acute pancreatitis. The severity of experimental pancreatitis was determined via serum lipase levels, morphometric evaluation and quantification of pancreatic edema/inflammation.
Hsp72 mice displayed ∼100-times Hsp72 overexpression, but no changes in the remaining chaperones. Robust Hsp72 signal was observed in pancreatic acini, but not in islets or ductal cells. In both models, elevated Hsp72 did not protect from development of acute pancreatitis and the pancreatitis-associated lung injury, but accelerated recovery from caerulein-induced tissue injury (lower lipase levels, edema, inflammation and necrosis 36 h after caerulein administration). The observed protective function of Hsp72 in caerulein-induced pancreatitis is likely due to an attenuated NF-κB signalling.
Hsp72 overexpression accelerates the recovery from acute pancreatitis and may represent a potential treatment strategy.
热休克蛋白（Hsp）72 是一种分子伴侣，可响应多种应激情况而上调，并具有普遍的细胞保护功能。Hsp72 水平升高与急性胰腺炎的保护有关；这一假说尚未在转基因小鼠模型中得到验证。
为了分析 Hsp72 在急性胰腺炎中的作用，在β-肌动蛋白启动子的控制下过表达大鼠 Hsp72（Hsp72 小鼠）的经过充分表征的转基因动物被用于研究钙调蛋白和精氨酸诱导的急性胰腺炎。通过血清脂肪酶水平、形态计量学评估和胰腺水肿/炎症的定量来确定实验性胰腺炎的严重程度。
Hsp72 小鼠显示出约 100 倍的 Hsp72 过表达，但其余伴侣蛋白没有变化。在胰腺腺泡中观察到强烈的 Hsp72 信号，但在胰岛或导管细胞中没有。在两种模型中，Hsp72 的升高都不能保护胰腺免受急性胰腺炎和胰腺炎相关的肺损伤的发展，但加速了钙调蛋白诱导的组织损伤的恢复（在给予钙调蛋白 36 小时后，脂肪酶水平、水肿、炎症和坏死降低）。Hsp72 在钙调蛋白诱导的胰腺炎中观察到的保护作用可能归因于 NF-κB 信号的减弱。
Hsp72 的过表达加速了急性胰腺炎的恢复，可能代表一种潜在的治疗策略。
