Heat Shock Protein 70 (HSP70) Reduces Hepatic Inflammatory and Oxidative Damage in a Rat Model of Liver Ischemia/Reperfusion Injury with Hyperbaric Oxygen Preconditioning
Hsing-Hsien Wu, Chien-Cheng Huang, Ching-Ping Chang, Mao-Tsun Lin, Ko-Chi Niu, Yu-Feng Tian
Department of Surgery, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
Med Sci Monit 2018; 24:8096-8104
Several clinical conditions can cause hepatic ischemia/reperfusion (I/R) injury. This study aimed to determine the mechanism of the protective effect of hyperbaric oxygen preconditioning (HBO₂P) on hepatic ischemia/reperfusion (I/R) injury in a rat model, and to investigate the effects on HBO₂P and I/R injury of blocking HSP70 using antibody (Ab) pretreatment.
MATERIAL AND METHODS: Male Sprague-Dawley rats underwent HBO₂P for 60 min at 2.0 atmosphere absolute (ATA) pressure for five consecutive days before surgical hepatic I/R injury, performed by clamping the portal vein and hepatic lobe. Four groups studied included: the non-HBO₂P+ non-I/R group, which underwent sham surgery (N=10); the non-HBO₂P + I/R group (N=10); the HBO₂P + I/R group (N=10); and the HBO₂P + HSP70-Ab + I/R group (N=10) received one dose of HSP70 antibody one day before hepatic I/R injury. Serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) and myeloperoxidase (MPO) were measured biochemically. Rat liver tissues were examined histologically.
RESULTS: In rats with hepatic I/R injury without HSP70 antibody pre-treatment, HBO₂P significantly reduced hepatic injury and levels of LDH, AST, ALT, TNF-α, IL-6, MDA, and MPO levels; in comparison, the group pre-treated with an antibody to inhibit HSP70 (the HBO₂P + HSP70-Ab + I/R group) showed significant reversal of the beneficial effects of HBO₂P on hepatic I/R injury (p<0.05).
CONCLUSIONS: In a rat model of hepatic I/R injury with HBO₂P, HSP70 reduced hepatic inflammatory and oxidative damage.
Keywords: HSP70 Heat-Shock Proteins, Hyperbaric Oxygenation, Liver Failure, Acute, Reperfusion Injury