HO-1在脓毒症大鼠心肌损伤中的作用及其对血清HMGB-1水平的影响  

Role of HO-1 in myocardial injury in septic rats and its effect on expression of HMGB1

作　　者：周仪华[1] 袁影[1] 盛志勇[1] 王舒[1] 王萌[1] 郭良云[1] ZHOU Yihua;YUAN Ying;SHENG Zhiyong;WANG Shu;WANG Meng;GUO Liangyun(The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China)

机构地区：[1]南昌大学第二附属医院,南昌330006

出　　处：《山东医药》2018年第46期29-33,共5页Shandong Medical Journal

基　　金：江西省科技计划项目(20151BBG70181);江西省卫生计生委科技计划项目(20175192)

摘　　要：目的探讨血红素加氧酶-1(HO-1)在脓毒症大鼠心肌损伤中的作用及其对血清高迁移率族蛋白B1(HMGB1)水平的影响。方法选择128只SD大鼠,随机分为假手术组、脓毒症组、钴原卟啉(CoppⅨ)组、锌原卟啉(ZnppⅨ)组,每组32只。CoppⅨ组和ZnppⅨ组均于造模前24 h分别给予腹腔注射HO-1增强剂Co PPⅨ10 mg/kg、HO-1抑制剂ZnppⅨ10 mg/kg,假手术组和脓毒症组不给药。脓毒症组、CoppⅨ组、ZnppⅨ组均采用盲肠结扎穿孔(CLP)法建立脓毒症模型。假手术组无菌状态下开腹找出盲肠后再将其还纳腹腔,不做CLP术。各组均于造模后0、6、12、24 h时处死大鼠8只,开腹经腹主动脉取血,ELISA法检测各组血清心肌损伤指标包括肌酸激酶同工酶(CK-MB)、肌钙蛋白-I(c Tn I)、B型脑钠肽(BNP)、心型脂肪酸结合蛋白(H-FABP),以及HMGB1、HO-1水平。采用Pearson相关系数法分析HMGB1与HO-1的相关性。结果 (1)各组血清心肌损伤指标水平比较:脓毒症组6、12、24 h时血清CK-MB、c Tn I、BNP、H-FABP水平均高于假手术组(P均<0. 05)。CoppⅨ组24 h血清CK-MB、c Tn I、BNP水平均低于脓毒症组,ZnppⅨ组6、12、24 h时血清CK-MB、c Tn I、BNP水平均高于脓毒症组(P均<0. 05)。ZnppⅨ组12、24 h时血清CK-MB、c Tn I、BNP水平均高于CoppⅨ组,6、12、24 h时血清H-FABP均高于CoppⅨ组(P均<0. 05)。(2)各组血清HMGB1、HO-1水平比较:脓毒症组6、12、24 h时血清HMGB1及HO-1水平均高于假手术组(P均<0. 05)。6、12、24 h时,CoppⅨ组血清HMGB1水平均低于脓毒症组、HO-1水平均高于脓毒症组,ZnppⅨ组血清HMGB1水平均高于脓毒症组、HO-1水平均低于CoppⅨ组(P均<0. 05)。(3)HMGB1与HO-1的相关性:脓毒症组、CoppⅨ组、ZnppⅨ组血清HMGB1与HO-1水平均呈负相关(r分别为-0. 342、-0. 415、-0. 437,P均<0. 05)。结论 HO-1对脓毒症大鼠的心肌具有保护作用,HO-1对心肌的保护作用可能与降低HMGB1水平有关。Objective To investigate the role of heme oxygenase-1( HO-1) in the myocardial injury of septic rats and its effect on high mobility group protein B1( HMGB1). Methods Totally 128 SD rats were randomly divided into four groups: the sham group,sepsis group,cobalt protoporphyrin( CoppⅨ) group,and zinc protoporphyrin( ZnppⅨ) group,with 32 in each group. At 24 h before the establishment of the model,the rats in the CoppⅨ group and ZnppⅨ group were injected intraperitoneally with 10 mg/kg HO-1 enhancer CoppⅨ and 10 mg/kg HO-1 inhibitor Znpp Ⅸ,respectively. The rats in the sham group and sepsis group were not administered. The sepsis models of the sepsis group,CoppⅨ group,and ZnppⅨ group were established by cecum ligation and perforation( CLP). In the sham group,the cecum was found under aseptic condition and then returned to the abdominal cavity without CLP. Eight rats were executed and 5-6 m L of blood was extracted from the abdominal aorta after laparotomy at 0,6,12,24 h after operation in each group. The serum MB isoenzyme of creatine kinase( CK-MB),troponin I( c Tn I),B-type brain natriuretic peptide( BNP),heart-type fatty acidbinding protein( H-FABP),HMGB1 and HO-1 levels were detected by enzyme-linked immunosorbent assay( ELISA) in each group. Pearson correlation coefficient method was used to analyze the correlation between HMGB1 and HO-1. Results(1)Comparison of serum myocardial injury indexes in each group: the levels of CK-MB,c Tn I,BNP,and H-FABP in the sepsis group at 6,12 and 24 h were all significantly higher than those in the sham group( all P < 0. 05). The levels of CKMB,c Tn I,and BNP in the CoppⅨ group at 24 h were significantly lower than those in the sepsis group,the levels of CKMB,c Tn I,and BNP in the ZnppⅨ group at 24 h were significantly higher than those in the sepsis group( all P < 0. 05).The levels of CK-MB,c Tn I,and BNP in the ZnppⅨ group at 12 and 24 h were significantly higher than those in the CoppⅨ group( all P < 0. 05).(2) Comparison of the levels of HMGB1 and H

关 键 词：脓毒症 心肌损伤 血红素氧合酶-1 高迁移率族蛋白B1 大鼠 

分 类 号：R631[医药卫生—外科学] R542.2[医药卫生—临床医学]