Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy.

ABSTRACT

OBJECTIVE: To explore the mechanisms whereby dexmedetomidine reversed lung injury in rats with toxic shock via inhibiting inflammation and autophagy. METHODS: Thirty-six specific pathogen-free male Sprague Dawley rats with were screened and randomly divided into three groups. Toxic shock was induced by intestinal leakage. The control group received no cecal ligation and the treatment group received dexmedetomidine hydrochloride. Lung tissue morphology was studied by hematoxylin-eosin staining. The expression levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The expression levels of beclin l and LC3 were measured, and the expression levels of apoptosis gene Bax and Bcl-2 were determined. The autophagosomes in lung cells were observed by transmission electron microscopy. Extracellular signal-regulated kinase (ERK) 1/2 expression was determined by Western blotting assays. RESULTS: The results showed that the W/D, total protein and myeloperoxidase (MPO) index in the toxic shock group were 5.45 ± 0.35, 3.21 ± 0.47 and 4.53 ± 0.36, respectively. The W/D (4.02 ± 0.67), total protein (2.01 ± 0.35) and MPO index (2.31 ± 0.59) were significantly lower in the dexmedetomidine group (p <0.05). Similarly, compared with the toxic shock group, the expression of p-ERK1/2 protein in the dexmedetomidine treatment group was significantly decreased (p <0.05). The expression levels of autophagy proteins beclin1 and LC3 in the dexmedetomidine treatment group were not significantly different from those of the control group (p >0.05). Transmission electron microscopy showed that the number of autophagic bodies in lung cells decreased. After induction with dexmedetomidine hydrochloride, the proapoptotic gene Bax was significantly downregulated in the cells. Bax expression levels in each group were 0.36 ± 0.12, 0.67 ± 0.06, and 0.32 ± 0.12, respectively. Compared with the control group, Bax expression in lung tissue significantly increased in the toxic shock group (p <0.05). CONCLUSION: Dexmedetomidine attenuates lung injury in toxic shock rats by inhibiting inflammation and autophagy.