ODN2088减轻线粒体DNA致脓毒症大鼠急性肺损伤  

Relief of ODN2088 for Acute Lung Injury in Rats with Sepsis Induced by Mitochondrial DNA

作　　者：唐甜[1] 李少军[1] 郭鹏飞[1] 杨林[1] 敖晓晓[1] 胡兰[1] 谭利平[1] Tang Tian;Li Shaojun;Guo Pengfei;Yang Lin;Ao Xiaoxiao;Hu Lan;Tan Liping(Children’s Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院,儿童发育疾病研究教育部重点实验室,国家儿童健康与疾病临床医学研究中心,儿童发育重大疾病国家国际科技合作基地,儿科学重庆市重点实验室,重庆400014

出　　处：《儿科药学杂志》2021年第3期1-6,共6页Journal of Pediatric Pharmacy

基　　金：重庆市科委前沿与应用基础计划项目,编号cstc2014jcyjA10032。

摘　　要：目的:探讨血浆线粒体DNA(mtDNA)含量与脓毒症大鼠急性肺损伤(ALI)程度的关系及选择性TLR9受体抑制剂ODN2088对脓毒症大鼠ALI的保护作用。方法:按随机数表法将80只大鼠分为假手术(sham)组、脓毒症(sepsis)组、脓毒症大鼠腹腔注射mtDNA 1.4 mg/kg(sepsis+mtDNA)组、脓毒症大鼠腹腔注射mtDNA 1.4 mg/kg+ODN20881 mg/kg(sepsis+mtDNA+ODN)组四组各20只。采用盲肠结扎穿孔手术(CLP)制备脓毒症合并ALI模型。术后6、12 h采集血液标本、肺泡灌洗液(BALF)和肺组织以检测血浆mtDNA及肺组织TLR9/p38MAPK表达水平。结果:与sham组相比,sepsis组大鼠病死率高,血浆mtDNA水平和肺组织TLR9/p38MAPK表达增加,ALI程度加重[肺损伤评分、BALF中炎症细胞、肺(湿-干)/干质量值和基因表达增加,P均<0.05)]。与sepsis组大鼠相比,sepsis+mtDNA组大鼠的病死率、血浆mtDNA水平、TLR9/p38MAPK表达增加,ALI程度加重(P均<0.05)。sepsis+mtDNA+ODN组大鼠较sepsis+mtDNA组病死率、血浆mtDNA水平、TLR9/p38MAPK表达及ALI程度降低(P均<0.05)。结论:血浆mtDNA水平与脓毒症致ALI有关,TLR9抑制剂ODN2088可减轻mtDNA诱导脓毒症大鼠ALI的程度。Objective:To probe into the correlation between plasma mitochondrial DNA(mtDNA)content and severity of acute lung injury(ALI)in rats with sepsis and the protective effects of selective Toll-like receptor 9(TLR9)inhibitor ODN2088 on ALI in rats with sepsis.Methods:According to the random number table method,80 rats were divided into the sham surgery(sham)group,sepsis(sepsis)group,intraperitoneal injection of mtDNA 1.4 mg/kg(sepsis+mtDNA)group and intraperitoneal injection of mtDNA 1.4 mg/kg+ODN20881 mg/kg(sepsis+mtDNA+ODN)group,with 20 rats in each group.The model of sepsis complicated with ALI was established by cecal ligation and perforation(CLP).After surgery of 6 and 12 h,blood samples,bronchoalveolar lavage fluid(BALF)and lung tissues were collected to detect plasma mtDNA and TLR9/p38 mitogen activated protein kinase(MAPK)expression levels in lung tissues.Results:Compared with the sham group,the sepsis group had higher mortality,increased levels of plasma mtDNA and TLR9/p38 MAPK expression in lung tissues,and increased ALI degree such as lung injury score,inflammatory cells in BALF,lung(wet-dry)/dry weight ratio and gene expression(P<0.05).Compared with the sepsis group,the mortality rate,plasma mtDNA,TLR9/p38MAPK expression and ALI degree increased in the sepsis+mtDNA group(P<0.05).Compared with the sepsis+mtDNA+ODN group,the mortality rate,plasma mtDNA,TLR9/p38MAPK expression and ALI degree decreased in the sepsis+mtDNA+ODN group(P<0.05).Conclusion:Plasma mtDNA is correlated with ALI induced by sepsis,and TLR9 inhibitor ODN2088 can relieve ALI in rats with sepsis induced by mtDNA.

关 键 词：脓毒症 急性肺损伤 线粒体DNA TLR9/p38受体 

分 类 号：R725.6[医药卫生—儿科]