- 作者：Kazushige Oishi ; M.D.&lowast ; ; Satoshi Hagiwara ; M.D. ; Ph.D.&dagger ; ; saku@oita-u.ac.jp ; Satoko Koga ; M.D.&lowast ; ; Satoshi Kawabe ; M.D.&lowast ; ; Takahiro Uno ; M.D. ; Ph.D.&lowast ; ; Hideo Iwasaka ; M.D. ; Ph.D.&dagger ; ; Takayuki Noguchi ; M.D. ; Ph.D.&dagger ;
- 关键词：hepatic ischemia-reperfusion injury ; EPC-K1 ; mitochondria ; necrosis ; apoptosis
- 刊名：Journal of Surgical Research
- 出版年：2012
- 期刊代码：299_00224804
- 类别：med
- 出版时间：July, 2012
- 卷：176
- 期：1
- 页码：164-170
- 文件大小：1212 K
Background
An important component of postoperative management includes alleviation of hepatic ischemia-reperfusion (I/R) injury, which commonly results from liver surgery. EPC-K1 is a hydroxyl radical scavenger reported to have mitigating effects on I/R injury in many organs. This study evaluates the effects of EPC-K1 on hepatic I/R injury.Materials and Methods
Rats were injected subcutaneously with either EPC-K1 (100 mg/kg) or saline. The hepatic artery and left branch of the portal vein were clamped for 45 min under general anesthesia. Indicators of liver function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and of liver tissue damage were evaluated after 6h and 24h of reperfusion. Serum levels of tumor necrosis factor (TNF)-伪, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein were measured, and apoptosis was quantified via caspase 3/7 activity and TUNEL assay.
Results
AST, ALT, and LDH levels increased significantly as a result of hepatic I/R injury, but were attenuated by EPC-K1 administration. Histologic findings revealed that normal structure of the hepatic parenchyma was maintained in rats pretreated with EPC-K1. TNF-伪, IL-6, and HMGB1 levels rose significantly after reperfusion, together with activation of the inflammatory response. However, EPC-K1 administration suppressed levels of inflammatory markers and attenuated the inflammatory response. Moreover, EPC-K1 administration prevented apoptosis as determined by inhibition of caspase 3/7 activity and a decrease in apoptotic cells.
Conclusions
Results demonstrate that EPC-K1 inhibits the inflammatory response and suppresses apoptosis during hepatic I/R injury. This suggests that EPC-K1 has hepatoprotective effects, and may be a valuable and novel therapeutic agent in the clinical setting.