ODN2088减轻线粒体DNA致脓毒症大鼠急性肺损伤

唐甜; 李少军; 郭鹏飞; 杨林; 敖晓晓; 胡兰; 谭利平

doi:10.13407/j.cnki.jpp.1672.108X.2021.03.001

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ODN2088减轻线粒体DNA致脓毒症大鼠急性肺损伤

基础研究 | 更新时间：2022-11-03

- 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
- 儿科药学杂志 2021年27卷第3期页码：1-6
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
  
  重庆市科委前沿与应用基础计划项目,编号cstc2014jcyjA10032
- DOI：10.13407/j.cnki.jpp.1672.108X.2021.03.001
  中图分类号：
- 纸质出版日期：2021，
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唐甜, 李少军, 郭鹏飞, 等. ODN2088减轻线粒体DNA致脓毒症大鼠急性肺损伤[J]. 儿科药学杂志, 2021,27(3):1-6.

Tang Tian, Li Shaojun, Guo Pengfei, et al. Relief of ODN2088 for Acute Lung Injury in Rats with Sepsis Induced by Mitochondrial DNA[J]. 2021,27(3):1-6.
唐甜, 李少军, 郭鹏飞, 等. ODN2088减轻线粒体DNA致脓毒症大鼠急性肺损伤[J]. 儿科药学杂志, 2021,27(3):1-6. DOI： 10.13407/j.cnki.jpp.1672.108X.2021.03.001.

Tang Tian, Li Shaojun, Guo Pengfei, et al. Relief of ODN2088 for Acute Lung Injury in Rats with Sepsis Induced by Mitochondrial DNA[J]. 2021,27(3):1-6. DOI： 10.13407/j.cnki.jpp.1672.108X.2021.03.001.

摘要

目的：探讨血浆线粒体DNA（mitochondrial DNA，mtDNA）含量与脓毒症大鼠急性肺损伤（acute lung injury，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：按随机数字表法将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+ODN2088 1 mg/kg（sepsis+mtDNA+ODN）组，每组各20只。采用盲肠结扎穿孔（CLP）制备脓毒症合并ALI模型。术后6 h、12 h采集血液标本、肺泡灌洗液（bronchoalveolar lavage fluid，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组比较，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）/干重比和基因表达增加，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组大鼠病死率、血浆mtDNA水平、TLR9/p38MAPK表达及ALI程度降低（P均<0.05）。结论：血浆mtDNA水平与脓毒症所致ALI有关，TLR9抑制剂ODN 2088可减轻mtDNA诱导的脓毒症大鼠ALI。

Abstract

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+ODN2088 1 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 [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mtDNATLR9/p38受体

Keywords

sepsisacute lung injurymitochondrial DNATLR9/p38 receptor

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