七氟醚预处理对糖尿病小鼠肝缺血-再灌注损伤的保护作用  

Protective effect of sevoflurane pretreatment on liver ischemic-reperfusion injury in diabetes mellitus mice

作　　者：欧珊珊[1] 韩玉湘[1] 肖笑雨[1] 杨禄坤[1] 朱颖娴[1] Ou Shanshan;Han Yuxiang;Xiao Xiaoyu;Yang Lukun;Zhu Yingxian(Department of Anesthesiology,the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China)

机构地区：[1]中山大学附属第五医院麻醉科,广东省珠海市519000

出　　处：《中华肝脏外科手术学电子杂志》2017年第6期509-512,共4页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：珠海市科技计划项目(2014D0401990015)

摘　　要：目的探讨七氟醚预处理对糖尿病小鼠肝缺血-再灌注损伤(IRI)的保护作用及其机制。方法雄性db/db 2型糖尿病模型小鼠24只,体重25~30 g/只,按随机数字表法分为假手术组(Sham组)、肝IRI组(IRI组)、七氟醚预处理组(S组)及七氟醚预处理+缺血-再灌注损伤组(SIR组),每组6只。Sham组仅暴露第一肝门,不阻断血流;IRI组肝门阻断30 min,恢复肝脏血流;S组吸入2.4%七氟醚120 min后行假手术;SIR组肝门阻断前吸入2.4%七氟醚120 min。检测各组血清中ALT、AST和肝组织超氧化物歧化酶(SOD)、丙二醇(MDA)等指标;Western blot法检测肝组织中核因子-κB(NF-κB)、细胞间黏附分子-1(ICAM-1)蛋白的表达。检测指标比较采用单因素方差分析和LSD-t检验。结果 SIR组的ALT、AST分别为(67±12)、(92±8)U/L,明显低于IRI组的(88±12)、(117±15)U/L(LSD-t=-4.18,-4.61;P<0.05)。SIR组的SOD活性为(126±12)U/mg,明显高于IRI组的(85±9)U/mg(LSD-t=6.53,P<0.05)。SIR组的MDA活性为(4.3±0.7)nmol/mg,明显低于IRI组的(6.7±1.1)nmol/mg(LSD-t=-5.85,P<0.05)。SIR组的NF-κB、ICAM-1蛋白的相对表达量分别为0.53±0.19、0.96±0.13,明显低于IRI组的0.97±0.13、1.29±0.11(LSD-t=-6.01,-5.63;P<0.05)。结论七氟醚预处理能减轻糖尿病小鼠IRI,其机制可能与增强自由基的清除能力、抑制NF-κB信号通路、降低肝脏内皮细胞ICAM-1的表达相关。Objective To investigate the effect and mechanism of sevoflurane pretreatment onthe liver ischemia-reperfusion injury(IRI)in diabetes mellitus mice model.Methods Twenty-four maledb/db mice with type2diabetes mellitus,weighed25-30g each,were divided into the sham surgery group(Sham group),liver IRI group(IRI group),sevoflurane pretreatment group(S group)and sevofluranepretreatment combined with ischemic-reperfusion group(SIR group),with6mice in each group.In Shamgroup,only the porta hepatis was exposed without blood occlusion.In IRI group,the hepatic portal occlusionwas performed for30min and restored afterward.In S group,sham operation was conducted120min afterinhalation of2.4%sevoflurane.In SIR group,inhalation of2.4%sevoflurane for120min was delivered beforehepatic portal occlusion.The levels of serum ALT,AST,superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue of each group were measured.The expression levels of nuclear factor-κB(NF-κB)and intercellular adhesion molecule-1(ICAM-1)proteins in liver tissue were detected by Western blot.The testedresults were compared using One-way ANOVA and LSD-t test.Results In SIR group,the level of serumALT and AST was respectively(67±12)and(92±8)U/L,significantly lower than(88±12)and(117±15)U/Lin IRI group(LSD-t=-4.18,-4.61;P<0.05).In SIR group,the SOD activity was(126±12)U/mg,significantlyhigher than(85±9)U/mg in IRI group(LSD-t=6.53,P<0.05).In SIR group,the MDA activity was(4.3±0.7)nmol/mg,significantly lower than(6.7±1.1)nmol/mg in IRI group(LSD-t=-5.85,P<0.05).In SIRgroup,the relative expression level of NF-κB and ICAM-1protein was respectively0.53±0.19and0.96±0.13,significantly lower than0.97±0.13and1.29±0.11in IRI group(LSD-t=-6.01,-5.63;P<0.05).ConclusionsSevoflurane pretreatment can mitigate IRI in diabetes mellitus mice,probably through enhancing theeliminating ability of free radicals,inhibiting NF-κB signaling pathway and down-regulating the expressionof ICAM-1in liver endothelial cells.

关 键 词：再灌注损伤 NF-κB 细胞粘附分子 超氧化物歧化酶 七氟醚 

分 类 号：R614[医药卫生—麻醉学]