Dexmedetomidine Ameliorates Lung Injury Induced by Intestinal Ischemia/Reperfusion by Upregulating Cannabinoid Receptor 2, Followed by the Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway
Meng Chen, Xue-Tao Yan, Ye Li, Jun-Jiao Tang, Zongze Zhang, Xianghu He
Abstract
Intestinal ischemia/reperfusion (I/R) is a clinical emergency, which often causes lung injury with high morbidity and mortality. Although dexmedetomidine has been identified to have a protective effect on lung injury caused by intestinal I/R, its specific mechanism is still elucidated. In recent years, the cannabinoid (CB 2 ) receptor pathway has been found to be involved in I/R injury of some organs. In the current study, we investigated whether the CB 2 receptor pathway contributes to the protective effect of dexmedetomidine on the intestinal I/R-induced lung injury in rats. Dexmedetomidine treatment upregulated the expression of CB 2 receptor and suppressed the I/R-induced increases in lung injury scores, inflammatory cell infiltration, lung wet/dry ratio, MPO activity, MDA level, inflammatory cytokines, and caspase-3 expression while augmenting SOD activity and Bcl-2 expression, indicating attenuation of lung injury. Dexmedetomidine treatment also increased the expression of Akt. The protective effects of dexmedetomidine treatment were reversed by the CB 2 receptor antagonist AM630 or the PI3K inhibitor wortmannin. And the CB 2 receptor antagonist AM630 also downregulated the expression of Akt. Thus, our findings suggest that treatment with dexmedetomidine provides a protective role against lung injury caused by intestinal I/R in rats, possibly due to the upregulation of the CB 2 receptor, followed by the activation of the PI3K/Akt pathway.