Plasma Mitochondrial DNA Provokes Acute Lung Injury Via Activation Of TLR9/p38 In Sepsis

Objective: To reveal the effects of plasma mtDNA levels on actue lung injury(ALI)and TLR9/p38 expression during sepsis.Methods: We subjected male Sprague-Dawley rats to cecal ligation and puncture(CLP)to establish septic models.Rats were randomly divide into 4 groups(n=15/group): animals undergoing a sham CLP(sham group);animals undergoing CLP(sepsis group);animals undergoing CLP and treat with mtDNA at 140 mg/kg of body weight(bw)(sepsis+mtDNA group);animals undergoing CLP treat with mtDNA 140 mg/kg and pretreated TLR9 specific inhibitor(ODN2088)100 mg/kg of bw(sepsis+mtDNA+ ODN group).Samples of blood,bronchoalveolar lavage fluid(BALF)of right lung and left lung tissue were harvested at different time point(6,12 hour post-CLP)for the detection of plasma mtDNA level,relative expression of TLR9/p38 mRNA in lung tissue and the indicators which represented ALI.Results: The model of moderate sepsis was successfully established by CLP,and moderate sepstic rat with ALI was confirmed by detecting the pathology of lung tissues,.Compared with sham group,sepsis group show high mortality,markedly increased level of plasma mtDNA,increased expression of TLR9/p38 mRNA in lung tissue and aggravated ALI.Rats in sepsis+mtDNA group compared with sepsis group those changes were aggravated.However,rats in sepsis+mt DNA+ODN group pretreated with specific TLR9 inhibitor,ODN 2088,can significantly decrease septic mortality,level of plasma mtDNA,expression of TLR9/p38 mRNA in lung tissue,and degree of ALI than rats in sepsis+mtDNA group.Conclusion: Plasma mtDNA promotes the progression of ALI in septic rat.This process is regulated by the TLR9/p38 signal pathway.