[The effect of dexmedetomidine on autophagy and apoptosis in intestinal ischemia reperfusion-induced lung injury].

OBJECTIVE

To investigate the protective effects of dexmedetomidine against autophagy and apoptosis in intestinal ischemia reperfusion (I/R)-induced lung injury.

METHODS

Twenty-four SD rats were randomly and equally divided into 4 groups according to the random number table: control group, I/R group, small dose of dexmedetomidine (D1) group and large dose of dexmedetomidine (D2) group. The model of lung injury was induced by occlusion of the superior mesenteric artery for 60 min followed by 12 h reperfusion. Rats in D1 and D2 groups received intravenous injection of dexmedetomidine at dose of 1 µg/kg and 5 µg/kg respectively. Rats in control and I/R groups were given same volume of normal saline. Pathological changes were detected by hematoxylin-eosin (HE) staining. The microtubule-associated protein 1 light chain 3(LC3)II/I ratio, Beclin-1, Bax and Bcl-2 expression were measured by Western blot. Cell apoptosis was assayed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while caspase-3 activity was evaluated by immunohistochemistry.

RESULTS

Significant infiltration of neutrophils and thickened alveolar walls were observed in the I/R group compared to the control group, which were improved by dexmedetomidine (5 µg/kg) treatment. Compared to the control group, the apoptosis cells [(69 ± 8) cells/field], LC3 II/I ratio(57 ± 8), Beclin-1(487%± 45%) and Bax (358% ± 37%) expression were markedly increased (P<0.05), while Bcl-2 (39% ± 5%) expression was decreased (P<0.05) in the I/R group. Compared to the I/R group, the apoptosis cells [(32 ± 5) cells/field], LC3 II/I ratio(27 ± 4), Beclin-1 (285%± 41%) and Bax (181% ± 25%) expression were markedly reduced (P<0.05), while Bcl-2 (91% ± 9%) expression was increased (P<0.05) in the D2 group.

CONCLUSIONS

Autophagy and apoptosis were activated in intestinal I/R-induced lung injury. Dexmedetomidine ameliorated intestinal I/R-induced lung injury via reducing autophagy and apoptosis.