Abstract
The aim of our study was to assess the effects of mitochondrial coenzyme Q (MitoQ) on sepsis-induced acute lung injury (ALI) and investigate its possible mechanisms. The cecal ligation and puncture (CLP) method was used to establish a septic ALI model. Rats were randomly divided into Con group, CLP group, MitoQ group, and MitoQ + LY294002 group. The survival rate of the rats was recorded, and the survival rate curve was plotted. Moreover, the ratio of wet/dry weight (W/D) in lung tissue was measured. The activity of myeloperoxidase (MPO) was measured by using the MPO colorimetric activity assay kit. The levels of high-mobility group box 1 (HMGB1) and interleukin-6 (IL-6), macrophage inflammatory protein 2 (MIP2), and keratinocyte chemoattractant (KC) were analyzed by ELISA. The histopathological changes were measured by HE staining, and the lung injury was scored. TUNEL assay was applied to detect the apoptotic cells in lung tissue. The protein expressions were detected by western blot. MitoQ increased the survival rate and alleviated pulmonary edema in septic ALI rats. In addition, MitoQ inhibited the MPO activity and decreased the levels of HMGB1 and IL-6. After treatment with MitoQ, alveolar wall edema, inflammatory cell infiltration, and red blood cell exudation were relieved. MitoQ inhibited cell apoptosis in lung tissue of septic ALI rats. Meanwhile, MitoQ treatment remarkedly increased the expression of p-Akt, p-GSK-3β, and p-mTOR but decreased Bax, caspase-3, caspase-9, Beclin-1, and LC-3II/LC-3I. The effects of MitoQ were significantly reversed by the PI3K inhibitor (LY294002). Our study demonstrated that MitoQ could protect sepsis-induced acute lung injury by activating the PI3K/Akt/GSK-3β/mTOR pathway in rats.
Highlights
Sepsis, a common acute and critical disease, is mainly characterized by sustained hypotension, metabolic acidosis, and systemic inflammatory response syndrome [1]
Our results revealed that Mitochondrial coenzyme Q (MitoQ) could protect acute lung injury in septic rats by activating the PI3K/Akt/ GSK-3β/mTOR pathway
Ese results suggested that MitoQ could improve the survival rate of septic acute lung injury (ALI) rats, while PI3K inhibitor LY294002 decreased the survival rate of septic ALI rats
Summary
A common acute and critical disease, is mainly characterized by sustained hypotension, metabolic acidosis, and systemic inflammatory response syndrome [1]. Due to the pulmonary susceptibility, acute lung injury (ALI) is one of the common lethal complications of sepsis [2]. Numerous studies focus on investigating the diagnosis and pathogenesis of sepsis-induced ALI, current treatment protocol is still limited. MitoQ has been reported to protect against renal ischemiareperfusion (I/R) injury [5]. Neuzil et al [6] have confirmed that MitoQ gives protection against I/R injury in the heart. It is reported that MitoQ could protect against organ damage in a rat model of sepsis [7]. The effect of MitoQ in sepsis-induced ALI has been poorly studied. Us, more researches are still needed to further investigate the mechanisms of MitoQ on sepsis-induced ALI The effect of MitoQ in sepsis-induced ALI has been poorly studied. us, more researches are still needed to further investigate the mechanisms of MitoQ on sepsis-induced ALI
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