【摘要】 目的:探讨血浆线粒体DNA(mt DNA)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mt DNA 1.4 mg/kg(sepsis+mt DNA)组、脓毒症大鼠腹腔注射mt DNA 1.4 mg/kg+ODN2088 1 mg/kg(sepsis+mt DNA+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mt DNA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mt DNA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+mt DNA组大鼠的病死率、血浆mt DNA水平、TLR9/p38MAPK表达增加,ALI程度加重(P均<0.05)。sepsis+mt DNA+ODN组大鼠较sepsis+mt DNA组病死率、血浆mt DNA水平、TLR9/p38MAPK表达及ALI程度降低(P均<0.05)。结论:血浆mt DNA水平与脓毒症致ALI有关,TLR9抑制剂ODN2088可减轻mt DNA诱导脓毒症大鼠ALI的程度。更多还原

【Abstract】 Objective: To probe into the correlation between plasma mitochondrial DNA( mt DNA) 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 mt DNA 1. 4 mg/kg( sepsis+mt DNA) group and intraperitoneal injection of mt DNA 1. 4 mg/kg+ODN2088 1 mg/kg( sepsis+mt DNA+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 mt DNA 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 mt DNA 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 mt DNA,TLR9/p38 MAPK expression and ALI degree increased in the sepsis+mt DNA group( P<0. 05). Compared with the sepsis+mt DNA+ODN group,the mortality rate,plasma mt DNA,TLR9/p38 MAPK expression and ALI degree decreased in the sepsis + mt DNA + ODN group( P < 0. 05). Conclusion: Plasma mt DNA is correlated with ALI induced by sepsis,and TLR9 inhibitor ODN2088 can relieve ALI in rats with sepsis induced by mt DNA.更多还原