Effect of suberoylanilide hydroxamic acid on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of suberoylanilide hydroxamic acid (SAHA) on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude.Methods Forty healthy male SpragueDawley rats,aged 2-3 months,weighing 240-280 g,transported from breeding grounds at an altitude of 1520 meters to the experimental station at an altitude of 3780 meters,were randomly divided into 4 groups (n =10each)sham operation group (group S),lethal hemorrhagic shock group (group LHS),normal saline group (group NS),and SAHA group.Anesthesia was induced with inhalation of 3% isoflurane and maintained with inhalation of 0.5%-1.0% isoflurane.Lethal hemorrhagic shock was induced by withdrawing blood from the femoral artery in groups LHS,NS and SAHA.Normal saline 0.25 ml and SAHA 7.5 mg/kg (0.25 ml) were injected intravenously over 2 min after completion of blood-letting in groups NS and SAHA,respectively.The survival rates with 3 h were recorded.Blood samples from femoral veins were taken before blood-letting,immediately after completion of blood-letting and at 3 h after completion of blood-letting (immediately after death if the survival time was less than 3 h) for determination of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) activities by the colorimetric method.Liver specimens were taken at 3 h after completion of blood-letting or immediately after death for examination of the pathological changes of the liver and for determination of c-Jun N-terminal kinase (JNK),phosphorylated-JNK (p-JNK) and caspase-3 expression and acetylation of H3K9 in liver tissues by Western blot.Results Compared with group S,the activities of serum AST,ALT and LDH were significantly increased in the other three groups (P ＜ 0.01).Compared with LHS and NS groups,the activities of serum AST,ALT and LDH were significantly decreased,the survival rate within 3 h and acetylation of H3K9 were increased,caspase-3 expression was down-regulated,and p-JNK/JNK ratio was decreased in group SAHA (P ＜ 0.05 or 0.01).The pathological changes of the liver were severe in LHS and NS groups and attenuated in SAHA group.Conclusion Administration of SAHA in early shock can significantly protect the liver after lethal hemorrhage in rats first entering high altitude,and increased acetylation of H3K9 and inhibition of the JNK/caspase-3 apoptotic pathway in liver tissues are involved in the mechanism.