Modified Mild Heat Shock Modality Attenuates Hepatic Ischemia/Reperfusion Injury
Modified Mild Heat Shock Modality Attenuates Hepatic Ischemia/Reperfusion Injury
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DOI：
10.1016/j.jss.2009.03.093
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发表时间：
2010-08-01
影响因子：
2.2
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
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作者：
Oba, Mariko;Suico, Ann;Kai, Hirofumi
背景资料。肝脏缺血再灌注(I/R)损伤是肝脏手术和移植引起的病理过程，至今仍是一个严重的临床问题。结果表明，热预适应对组织I/R损伤有保护作用。但体温过高可能既费力又耗时。或者，据报道，温和电刺激(MES)的应用在临床环境中对几种内科疾病具有积极效果。因此，我们将短期轻度热休克(HS)和MES相结合的方法加以改进，并评价HS+MES预处理对I/R所致肝损伤的影响。材料与方法C57BL/6J小鼠随机分为假手术组和对照组，分别给予HS(42℃)和(或)MES(12V)处理2 0min，1wk内隔日1次。最后一次治疗后，造成小鼠肝脏缺血30或60min，再灌注6h，通过检测血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平来评价肝损伤程度。采用实时定量聚合酶链式反应和免疫印迹法检测肝组织中促炎症细胞因子和热休克蛋白72的表达。HS+MES可抑制肝脏I/R所致的血清AST、ALT的释放及部分促炎细胞因子的mRNA水平。此外，HS+MES还可上调小鼠肝脏HSP72的表达。HS+MES预适应可能通过诱导HSP72减轻肝脏I/R损伤，并抑制小鼠肝脏促炎细胞因子的表达。(C)2010 Elsevier Inc.保留所有权利。
Background. Hepatic ischemia/reperfusion (I/R) injury is a pathologic process caused by hepatic surgery and transplantation, and still remains a severe clinical problem. It was shown that preconditioning by hyperthermia might protect tissues against I/R injury. But hyperthermia could be laborious and time-consuming. Alternatively, the application of mild electrical stimulation (MES) has been reported to have positive effects in clinical settings on several medical ailments. Thus, we modified the preconditioning approach by combining short-term mild heat shock (HS) and MES, and evaluated the effect of HS + MES pretreatment on hepatic injury induced by I/R.Materials and Methods. C57BL/6 J mice were sham treated or treated three times with HS (42 degrees C) and/or MES (12 V) for 20 min, carried out every other d within 1 wk. After the last treatment, mice were subjected to hepatic ischemia for 30 or 60 min and reperfusion for 6 h. Liver injury was assessed by evaluating the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The expressions of pro-inflammatory cytokines and heat shock protein (Hsp) 72 in liver tissues were also assessed by real-time PCR and Western blotting analyses, respectively.Results. HS + MES pretreatment suppressed the hepatic I/R-induced release of serum AST and ALT and the mRNA levels of some pro-inflammatory cytokines. In addition, HS + MES up-regulated the expression of Hsp72 in mice liver.Conclusions. HS + MES preconditioning ameliorated hepatic I/R injury possibly through Hsp72 induction, and suppressed pro-inflammatory cytokine expression in mice liver. (C) 2010 Elsevier Inc. All rights reserved.