Modified mild heat shock modality attenuates hepatic ischemia/reperfusion injury.
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.


METHODS
C57BL/6J mice were sham treated or treated three times with HS (42 degrees C) and/or MES (12V) for 20min, carried out every other d within 1 wk. After the last treatment, mice were subjected to hepatic ischemia for 30 or 60min and reperfusion for 6h. 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.
Oba
Mariko
M
Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, Kumamoto, Japan.
Suico
Mary Ann
MA
Morino
Saori
S
Yano
Shuichiro
S
Matsuno
Takashi
T
Koga
Tomoaki
T
Sato
Takashi
T
Shuto
Tsuyoshi
T
Kai
Hirofumi
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D005784:Gene Amplification; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics; D006358:Hot Temperature; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D008099:Liver / Q000293:injuries / Q000473:pathology / Q000601:surgery; D008102:Liver Circulation; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000453:epidemiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D017931:DNA Primers; D050884:HSP72 Heat-Shock Proteins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase