Effects of BML-111 on liver injury and inflammatory responses after hemorrhagic shock and resuscitation in rats

Abstract

Objective To investigate the effects of BML-111 on liver injury and inflammatory responses after hemorrhagic shock and resuscitation in rats. Methods Forty male SD rats were randomly divided into 5 groups: sham group, hemorrhagic shock-resuscitation(HS-R) group and BML1111-3 group.The serum liver function-related index was monitored by automatic biochemical analyzer.Liver protein levels of inducible nitric oxide synthase(iNOS)and endothelin-1(ET-1) were detected by enzyme linked immunosorbent assay(ELISA).The protein levels of cytoplasmic p65, inhibitory κB(IκB)-α, tumor necrosis factor-α(TNF-α) and nuclear p65 were detected by Western blotting. Results As compared with HS-R group, 0. 5, 1. 0 and 2. 0 mg/kg of BML-111 treatments respectively decreased serum alanine transaminase(ALT) levels by 22. 7%, 37. 1% and 46. 1% respectively after hemorrhagic shock and resuscitation(P< 0. 05). As compared with hemorrhagic shock-resuscitation group, 0. 5, 1. 0 and 2. 0 mg/kg of BML-111 treatments respectively decreased serum aspartate aminotransferase(AST)levels by 40. 6%, 52. 7% and 60. 9% respectively after hemorrhagic shock and resuscitation(P< 0. 05).As compared with hemorrhagic shock-resuscitation group, 0. 5, 1. 0 and 2. 0 mg/kg of BML-111 treatments respectively decreased serum lactate dehydrogenase(LDH) levels by 39. 4%, 46. 4% and 58. 2% respectively after hemorrhagic shock and resuscitation(P< 0. 05). Additionally, treatments of BML-111 also decreased hepatic levels of iNOS and ET-1, and attenuated the activation of hepatic NF-κB-p65 signaling pathway after hemorrhagic shock and resuscitation(P< 0. 05). Conclusion BML-111 can attenuate liver injury and inflammatory responses after hemorrhagic shock and resuscitation by inhibiting NF-κB-p65 signaling pathway. Key words: BML-111; Hemorrhagic shock; Liver; Inflammatory response