重组人白细胞介素-11对脓毒症大鼠肺损伤的保护作用  

Protective effect of recombinant human interleukin-11 on lung injury in the rats with sepsis

作　　者：尹江宁[1] 殷雪平[2] 陈义坤[1] 任国庆[1] Yin Jiang-ning;Yin Xue-ping;Chen Yi-kun;Ren Guo-qing(Emergency Department,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China)

机构地区：[1]江苏大学附属医院急诊科,江苏镇江212001 [2]江苏大学附属医院血液净化中心,江苏镇江212001

出　　处：《中国急救医学》2020年第2期164-169,共6页Chinese Journal of Critical Care Medicine

基　　金：镇江市社会发展项目(SH2018054);江苏大学附属医院人才启动基金(jdfyRC2018012)。

摘　　要：目的观察重组人白细胞介素-11(rhIL-11)对脓毒症大鼠肺损伤的保护作用,并探讨其可能机制.方法将80只SD大鼠随机分为正常组10只、假手术组10只、脓毒症组30只、rhIL-11治疗组30只.采用盲肠结扎穿孔法(CLP)建立脓毒症大鼠模型.术前治疗组给予rhIL-11[500μg/(kg·d)]皮下注射;脓毒症组、假手术组和正常组大鼠均注射平衡溶液[10mL/(kg·d)].酶联免疫吸附法测定术前和术后6、12和24h血清肿瘤坏死因子-α(TNF-d)、白细胞介素-6(IL-6)和白细胞介素-11(IL-11)浓度.CLP后24 h取肺标本,进行组织病理学分析.Western blot检测肺组织中p-IκBα、Bcl-2、Bax及JAK1、STAT3蛋白的表达.实时定量(RT-PCR)法检测Bax mRNA表达浓度.结果①造模后12、24 h治疗组血清IL-6浓度(pg/mL)(307.4±48.6、204.2±31.5)明显低于脓毒症组(644.8±88.7、570.4±66.3)(P<0.05),治疗组血清TNF-α浓度(pg/mL)(319.2±32.8、258.6±40.5)明显低于脓毒症组(382.1±54.7、324.3±30.0)(P<0.05),治疗组血清IL-11浓度(pg/mL)(761.0±109.3、672.4±99.5)明显高于脓毒症组(618.2±71.7、530.6±90.2)(P<0.05);②治疗组Bax mRNA及蛋白Bax、p-IκBα的表达分别为(0.46±0.09、0.82±0.19、0.61±0.20),与脓毒症组(0.78±0.12、1.19-±0.33、0.82±0.22)比较明显降低(P<0.05);治疗组Bcl-2表达(0.65±0.19)与脓毒症组(0.41±0.11)比较明显增加(P<0.05).③治疗组JAK1和STAT3蛋白表达指数(2.37±0.26、2.39±0.25)明显高于其他组(P<0.05).④与脓毒症组比较,治疗组肺组织损伤和坏死明显减少;治疗组大鼠肺组织病理学评分(4.43±1.07)分明显优于脓毒症组(6.91±1.18)分(P<0.05).结论rhIL-11对脓毒症大鼠肺损伤具有保护作用,其机制可能与通过JAK1/STAT3通路的调控,抗凋亡并抑制炎症反应有关.Objective To evaluate the protective effect of recombinant human interleukin-11(rhIL-11)on lung injury in rat models of sepsis,and to explore the underlying mechanism.Methods Eighty SD rats were divided into rhIL-11 treatment group(30 rats),sepsis group(30 rats),normal group(10 rats)and sham group(10 rats)randomly.Septic rat models were established by cecal ligation and perforation(CLP).RhIL-11 treatment group was given subcutaneous injection of rhIL-11[500μg/(kg·d)].However,the rats of sepsis group or normal group and sham group were injected with balanced solution[10 mL/(k g·d)].Serum tumor necrosis factor-alpha(TNF-a),interleukin-6(IL—6)and interleukin—11(IL-11)levels were measured by enzyme linked immunosorbent assay at 6,12 and 24 h after the treatment and before the treatment.Samples of lung were collected at 24 h after CLP to perform histopathological study and molecular analysis.The mRNA expressions of Bax were evaluated by transcription-polymerase chain reaction.The protein expressions of JAK1 and STAT3 in lung were assayed by Western blot.Results(I)Inflammatory cytokines were lower in the treatment group[IL-6(307.4±48.6)p g/mL,(204.2±31.5)pg/mL,TNF-ct(319.2±32.8)p g/m L,(258.6±40.5)pg/m L]than in the sepsis group[IL-6(644.8±88.7)pg/mL,(570.4±66.3)pg/mL,TNF—a(382.1±54.7)pg/m L,(324.3±30.0)pg/m L]at 12,24 h after model establishment(P<0.05).But IL-11 was obviously higher in the treatment group[(761.0±109.3)pg/m L,(672.4±99.5)pg/m L]than in the sepsis group[(618.2±71.7)pg/mL,(530.6±90.2)pg/m L,P<0.05].②The expression of Bax mRNA and Bax,p-IkBcx were lower in treatment group(0.46±0.09,0.82±0.19,0.61±0.20)compared with sepsis group(0.78±0.12,1.19±0.33,0.82±0.22,P<0.05).Bel-2 increased obviously in the treatment group(0.65±0.19)compared with the sepsis group(0.41±0.11).③The level of JAK1 and STAT3 protein expression in the treatment group(2.37±0.26,2.39±0.25)were observably higher than those in other three groups(P<0.05).④The pulmonary injury[(4.43±1.07)scores]and necrosi

关 键 词：重组人白细胞介素-11(rhIL-11) 脓毒症 炎症 JAK1/STAT3信号通路 BAX BCL-2 

分 类 号：R459.7[医药卫生—急诊医学]