微小RNA-155对内毒素血症幼鼠肝脏白细胞介素-1受体相关激酶-1、4mRNA表达的影响  

Effects of microRNA-155 on interleukin-1 receptor-associated kinase 1 and 4 mRNA expression in liver injury of endotoximia mice

作　　者：吕鑫[1] 张育才[1] 崔云[1] 任玉倩 李芮[1] 戎群芳[1] 

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院重症医学科,200040

出　　处：《中国小儿急救医学》2015年第3期156-160,164,共6页Chinese Pediatric Emergency Medicine

摘　　要：目的 探讨微小RNA-155（microRNA-155,miRNA-155）对内毒素血症幼年小鼠肝组织白细胞介素（interleukin,IL）-1受体相关激酶（interleukin-1 receptor-associated kinase,IRAK）-1 mRNA及 IRAK-4 mRNA表达的影响.方法 120只3～5周龄雄性BALB/c小鼠,随机数字表法随机分为内毒素组、miRNA-155抑制物组和对照组,每组各40只.miRNA-155抑制物组注射内毒素前于尾静脉注射miRNA-155抑制物180mg/（kg＆#183;d）.内毒素组和miRNA-155抑制物组腹腔注射内毒素20 mg/kg,对照组腹腔注射等容量生理盐水.注射内毒素后6、12、24、48 h（每亚组各10只）分别处死,留取肝脏组织标本.实时荧光定量PCR法检测肝组织miRNA-155、IRAK-1 mRNA、IRAK-4 mRNA表达,ELISA法测定肝组织肿瘤坏死因子（tumor necrosis factor,TNF）-α、IL-1和IL-10的表达;观察肝组织病理变化.结果 内毒素组及miRNA-155抑制物组小鼠肝脏miRNA-155表达较对照组升高,在6h达峰值,后逐渐下降,在48 h各组水平趋于一致,各组间比较在6h、12 h、24 h差异有统计学意义（P＜0.05）.内毒素组及miRNA-155抑制物组IRAK-1 mRNA及IRAK-4 mRNA表达较对照组水平升高,miRNA-155抑制物组较内毒素组降低,12、24、48 h时间点,3组间小鼠肝组织IRAK-1 mRNA及IRAK-4 mRNA表达水平的差异有统计学意义（P＜0.05）.内毒素组及miRNA-155抑制物组肝组织TNF-α、IL-1、IL-10水平较对照组升高,miRNA-155抑制物组较内毒素组TNF-α、IL-1、IL-10水平下降,各组间比较差异有统计学意义（P＜0.05）.HE染色下观察肝组织病变：内毒素组小鼠肝组织病理损伤出现早,损伤程度重,miRNA-155抑制物组病理损伤程度相对较轻.结论 抑制内毒素血症小鼠miRNA-155,小鼠肝组织IRAK-1 mRNA及IRAK-4 mRNA表达下降,炎症因子水平下降,肝脏病理损伤减轻.Objective To explore the protective effect of rnicroRNA （miRNA）-155 inhibitor on interleukin-1 receptor-associated kinase （IRAK）-1 mRNA and IRAK-4 mRNA in endotoximia induced liver injury in mice.Methods One hundred and twenty male BALB/c mice were randomly divided into healthy control group（n =40）,endotoximia group （n =40） and miRNA-155 inhibitor group （n =40）.Each group were divided into 6 h,12 h,24 h,48 h subgroups,each of which consisted of 10 mice.The mice in miRNA-155 inhibitor group were administered with miRNA-155 inhibitor[80 mg（kg ＆#183;d）] via tail vein injection before lipopolysaccharide （LPS） administration while the other two groups treated with normal saline,following 24 hours,model of endotoximia mice was produced by injection of LPS intraperitoneally.At 6 h,12 h,24 h,48 h after LPS exposure,the experimental mice were sacrificed and the liver tissue samples were collected.Histopathological changes,the expression of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,tumor necrosis factor （TNF）-α,IL-1,IL-10 were detected.Results LPS exposure resulted in increase of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,TNF-α,IL-1 and IL-10 in both endotoximia group and miRNA-155 inhibitor group compared to the control group,miRNA-155 inhibitor resulted in decrease of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,TNF-α,IL-1 and IL-10 in miRNA-155 inhibitor group compared to the endotoximia group.There were significant differences of miRNA-155 expression at 12 h,24 h,48 h after LPS exposure among 3 groups （P 〈 0.05）.Both IRAK-1 mRNA and IRAK-4 mRNA showed significant differences at 12 h,24 h,48 h.Turning to inflammation factors,differences were found among 3 groups at all time points （P 〈 0.05）.At light-scope,there was improvement in sepsis associated liver injury in miRNA-155 inhibitor group compared to endotoximia group.Conclusion miRNA-155 inhibitor administration appears to down regulate IRAK-1 mRNA and IRAK-4 mRNA expression and further deduce the excessive inflammatory and anti-inflammatory react

关 键 词：微小RNA-155 白细胞介素-1 受体相关激酶 MRNA 白细胞介素-4 受体相关激酶 MRNA 肝损伤 内毒素 RNA干扰 小鼠 

分 类 号：R965[医药卫生—药理学]