Carbazochrome attenuates acute lung injury in septic rats by inhibition of Parkin-mediated mitochondrial autophagy

Abstract

ObjectivesWe aimed to explore the effect of carbazochrome on acute lung injury in septic rats. MethodsMale Wistar rats were randomly divided into sham operation operation group, sepsis group and carbazochrome groups (8 mg/kg, 40 mg/kg, 80 mg/kg). After cecal ligation and puncture (CLP) method was used to establish a sepsis model, different doses of carbazochrome or 0.9% normal saline were injected intraperitoneally. The survival curve of rats was drawn. Micro-CT examination of the lungs was performed 24 h after the operation. Arterial blood samples were collected for blood gas detection. ResultsCompared with sepsis group, the survival rate, arterial partial pressure of oxygen and oxygenation index were increased (P < 0.01), lung index and pulmonary vascular permeability were decreased (P < 0.05) in the carbazochrome group. The lung lesions and injuries were more severe in the sepsis group, which were improved by carbazochrome treatment (P < 0.05). Additionally, the pathological changes of mitochondria of septic rats were serious, and JC-1 value decreased, which were reversed by carbazochrome treatment (P < 0.05). The apoptosis rate of lung cells was significantly increased (P < 0.01), and the level of mitochondrial autophagy was enhanced in sepsis rats, while those changes were ameliorated by carbazochrome treatment (P < 0.05). Moreover, compared with sham operation group, the protein expressions of Parkin and Drp1 and the ratio of LC3 II/LC3 I were increased, and the protein expression of Mfn2 was decreased, while those changes were ameliorated by carbazochrome treatment (P < 0.05). ConclusionCarbazochrome attenuates acute lung injury in septic rats by inhibition of Parkin-mediated mitochondrial autophagy.