ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury

作者：Choi Dae Eun; Jeong Jin Young; Choi Hyunsu; Chang Yoon Kyung; Alm Moon Sang; Ham Young Rok; Na Ki Ryang; Lee Kang Wook

来源：Surgery, 2017, 161(2): 444-452.

DOI：10.1016/j.surg.2016.07.028

Background. Although hypothermia attenuates the renal injury induced by ischemia-reperfusion, the detailed molecular pathway(s) involved remains unknown. ERK phosphorylation is known to protect against ischemia-reperfusion injury. Also, it has been reported that hypothermia may induce ERK phosphorylation in the heart and brain. We evaluated the role played by ERK in hypothermic protection against renal ischemia-reperfusion injury.
Methods. C57B1/6 mice were divided into the following groups: sham-operated (cold, 32 degrees C) vs normal temperature (37 degrees C); ischemia-reperfusion mice (32 degrees C vs 37 degrees C); and PD98059-or vehicle-treated ischemia-reperfusion mice (32 degrees C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24 hours after ischemia-reperfusion injury. Functional and molecular markers of kidney injury were evaluated. To explore the molecular mechanism involved the expression levels of renal HIF-1 and associated proteins were evaluated.
Results. The blood urea nitrogen (BUN) and serum creatinine (s-Cr) levels and the histologic renal injury scores were significantly lower in 32 degrees C ischemia-reperfusion than 37 degrees C ischemia-reperfusion kidneys (allP values < .05). The expression levels of Bax and caspase-3 and the extent of TUNEL and 8-OHdG cell positivity decreased, whereas the renal Bcl-2 level increased, in 32 degrees C ischemia-reperfusion compared to 37 degrees C ischemia-reperfusion mice. The extent of renal ERK phosphorylation was significantly higher in ischemiareperfusion than sham-operated kidneys. Also, ERK phosphorylation was significantly increased in the kidneys of 32 degrees C compared to 37 degrees C ischemia-reperfusion mice. PD98059 treatment of 32 degrees C ischemiareperfusion mice significantly decreased the renal H1F-1 level (P < .05) and increased the BUN, s-Cr, renal Bax, and caspase-3 expression levels; the tissue injury score; and the proportions of TUNEL-and 8-0HdGpositive cells. PD98059 also increased the renal Bcl-2 level in such mice.
Conclusion. Hypothermia attenuates the renal apoptosis and oxidative stress induced by ischemiareperfusion via a mechanism involving ERK phosphorylation.

• 出版日期2017-2