抗HMGB1单抗对小鼠脑缺血—再灌注损伤后IL-1β IL-6表达的影响  

Effect of anti-HMGB1 monoclonal antibody on the expression of IL-1β and IL-6 after brain ischemia reperfusion

作　　者：孙恺[1] 谢楠[2] 陶庆霞 王翀[3] 

机构地区：[1]潍坊医学院,2013级研究生山东潍坊261053 [2]徐州市中心医院,江苏徐州221000 [3]济宁医学院附属济宁市第一人民医院,山东济宁272011

出　　处：《济宁医学院学报》2015年第5期313-317,共5页Journal of Jining Medical University

摘　　要：目的探讨抗高迁移率族蛋白B1(high mobility group protein box 1,HMGB1)单抗(mAb)对小鼠脑缺血-再灌注损伤后炎症因子IL-1β、IL-6mRNA表达的影响。方法采用大脑中动脉阻断术(MCAO)建立小鼠脑缺血-再灌注损伤模型,造模成功后随机分为假手术组(sham组),脑缺血-再灌注组(I/R组),抗HMGB1单克隆抗体组(mAb组)和单抗对照组(control IgG组),mAb组小鼠经尾静脉注射30μg/g抗HMGB1单抗,control IgG组尾静脉注射同等剂量小鼠IgG;ELISA测定血清HMGB1浓度;干湿重法测定脑水肿程度;HE染色观察病理形态学变化;实时荧光定量PCR测定小鼠脑组织IL-1β,IL-6mRNA的表达量变化。结果1)ELISA测得I/R小鼠血清HMGB1的浓度为(47.75±3.667)ng/ml,明显高于sham组小鼠的HMGB1浓度(5.353±1.489)ng/ml(t=10.71,P<0.001);2)I/R组、mAb组脑组织含水量分别为(78.34±2.836)%、(65.09±1.934)%,I/R组显著高于mAb组(t=3.86,P<0.05);3)mAb组脑组织缺血损伤病理学改变明显轻于I/R组;4)I/R组IL-1βmRNA表达量(0.783±0.028)显著高于mAb组(0.417±0.047)(t=22.08,P<0.01),mAb组IL-6MRNA表达量(0.655±0.052)与I/R组(0.650±0.052)相比,无明显差异(t=0.089,P>0.05)。结论 HMGB1介导脑缺血-再灌注损伤机制中炎症反应过程,小鼠静脉注射抗HMGB1单抗可有效保护受损脑组织。Objective To investigate the effect of anti-HMGB1 monoclonal antibody on the expression of IL-1βand IL-6 after brain ischemia reperfusion.Methods The models were established by an intraluminal suture method to induce brain ischemia reperfusion injury.Animals were randomly divided into sham group,ischemia reperfusion （I/R）group,anti-HMGB1 monoclonal antibody （mAb）group （30μg/g）,and IgG control group.After that,serum HMGB1 levels were measured by ELISA analysis,Brain edema was investigated by dry-wet method.H＆amp;E staining was used to observe pathologic changes,and the expressions of IL-1βand IL-6 were tested by real-time PCR.Re-sults 1 ）The concentrations of serum HMGB1 in I/R group[（47.75 ±3.667 ）ng/ml]were significantly higher than that of sham group[（5.353 ±1.489）ng/ml]（t =10.71,P 〈0.0001 ）.2）The brain water content in I/R group[（78.34±2.836）%]was higher than mAb group [（65.09±1.934）%]（t =3.86,P 〈0.05）;3）I/R group presented worse damage to the brain compared with mAb group showed by H＆E staining.4）The expressions of IL-1βin I/R group （0.783±0.028）were significantly increased by contrast with mAb group （0.417 ±0.047）（t =22.08,P 〈0.01 ）.There was no significant difference in the expressions of IL-6 between the 2 groups （t =0. 089,P 〉0.05）.Conclusion HMGB1 mediates the process of inflammatory reaction in brain ischemia reperfusion. Anti-HMGB1 monoclonal antibody contributes to the protection against ischemia reperfusion injury in brain.

关 键 词：脑缺血-再灌注损伤 炎症因子 高迁移率族蛋白 B1 单克隆抗体 (HMGB1) 

分 类 号：R743[医药卫生—神经病学与精神病学]