| 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。 |
| 关键词: 脓毒症 急性肺损伤 mtDNA TLR9/p38受体 |
| DOI：doi:10.13407/j.cnki.jpp.1672.108X.2021.03.001 |
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| 基金项目:重庆市科委前沿与应用基础计划项目,编号cstc2014jcyjA10032 |
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| Relief of ODN2088 for Acute Lung Injury in Rats with Sepsis Induced by Mitochondrial DNA |
| 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) |
| 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. |
| Key words: sepsis acute lung injury mitochondrial DNA TLR9/p38 receptor |
