脂氧素受体激动剂BML-111缓解大鼠失血性休克复苏后肝脏损伤和炎性反应  

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

作　　者：黄晓雷[1] 陈岱莉[1] 齐晓非[1] 曹君[1] 李元涛[1] 

机构地区：[1]南方医科大学附属深圳妇幼保健院麻醉科,深圳518028

出　　处：《中华实验外科杂志》2015年第6期1329-1332,共4页Chinese Journal of Experimental Surgery

摘　　要：目的 观察脂氧素受体激动剂BML-111对大鼠失血性休克诱发的肝功能损伤和炎性反应的影响.方法 将40只雄性SD大鼠随机分为5组：假手术组、失血性休克-复苏组、低剂量BML-111＋失血性休克-复苏组、中剂量BML-111＋失血性休克-复苏组、高剂量BML-111＋失血性休克-复苏组.全自动生化分析仪检测血浆中肝功能相关指标.酶联免疫吸附试验（ELISA）法检测肝组织诱导型一氧化氮合酶（iNOS）及内皮素-1（ET-1）表达水平.Western blot法检测肝组织胞质p65、κB抑制蛋白（IκB）-α、肿瘤坏死因子-α（TNF-α）及胞核p65蛋白表达水平.结果 0.5、1.0、2.0 mg/kg BML-111分别使失血性休克复苏大鼠血浆谷丙转氨酶（ALT）水平下降22.7％、37.1％和46.1％（P＜0.05）;0.5、1.0、2.0 mg/kg BML-111分别使失血性休克复苏大鼠血浆谷草转氨酶（AST）水平下降40.6％、52.7％和60.9％ （P ＜0.05）;0.5、1.0、2.0 mg/kg BML-111分别使失血性休克复苏大鼠血浆乳酸脱氢酶（LDH）水平下降39.4％、46.4％和58.2％ （P ＜0.05）.同时,BML-111缓解失血性休克-复苏大鼠肝脏iNOS和ET-1表达水平升高和核因子-κB （NF-κB）-p65信号通路激活（P＜0.05）.结论 脂氧素受体激动剂BML-111可通过抑制NF-κB-p65缓解大鼠失血性休克复苏后肝脏损伤和炎性反应.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.

关 键 词：BML-111 失血性休克 肝脏 炎性反应 

分 类 号：R459.7[医药卫生—急诊医学]