关键词: 右美托咪定, 肺缺血再灌注, TLR4, 炎症因子

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 (n=10), including sham group (S group), Pulmonary 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 30min, and then reperfusion for 3 h. The lung tissue was observed by HE staining. RT-qPCR detected the expression of TLR4 mRNA, and ELISA measured the TNF-α, IL-6 and IL-1, including WT and TLR4?/?, levels. WB measured the expression of NLRP3 in lung tissue in both WT and TLR4?/?. Results Dex significantly improved the pathological damage of LIRI, reduced 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 this study did not found these cytokines was 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 protecting lung from LIRI.

Key words: Dexmedetomidine, Lung ischemia-reperfusion, TLR4, inflammation cytokines