Dexmedetomidine decreases TLR4 expression to alleviate lung ischemia/reperfusion injury in mice / 基础医学与临床

ABSTRACT

Objective To investigate the protective mechanism of dexmedetomidine ( Dex) hydrochloride to lung ischemia/reperfusion injury ( LIRI) in mice. Methods The wild type ( WT) and Toll-like receptor 4 knockout ( TLR4-/-) C57BL/6 Balb/c female mouse randomly divided into four groups sham group ( S group) , pulmona-ry ischemia/reperfusion group ( I/R group) , normal saline group ( NS group) and Dex group ( D group) . In S group, the chest was opened only, but in I/R group, NS group and D group, model of lung ischemia/reperfusion injury in mice was made by clamping left pulmonary hilum for 30 min, and then reperfusion for 3 h. The lung tis-sue was observed by HE staining. RT-qPCR detected the expression of TLR4 mRNA, and ELISA measured the TNF-α, IL-6 and IL-1 levels, including WT and TLR4-/-. Western blot measured the expression of NLRP3 in lung tissue in both WT and TLR4-/-. Results Dex significantly decreased the pathological damage of LIRI, re-duced the expression of levels of TLR4 mRNA and the production of inflammatory cytokines ( P＜0.01) , and also suppress production and activation of NLRP3 ( P＜0.01) in lung ischemia/reperfusion tissue in WT mice. But no cytokines was found to be inhibited in TLR4-/- mice. Conclusions Dex may decrease the release of a variety of pro-inflammatory factors and inhibit production and activation of NLRP3 inflammasome by TLR4, thereby protect lung against LIRI.