ABSTRACT
Objective To evaluate the role of α2A adrenergic receptor (α2AAR) in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation (H/R)caused injury to alveolar type Ⅱ epithelial cells.Methods Type Ⅱ] alveolar epithelial cells of rats RLE6TN cells cultured in vitro were divided into 4 groups (n =6 each) using a random number table method:control group (group C),H/R injury group (group H/R),dexmedetomidine group (group D) and α2A AR small interfering RNA (siRNA) plus dexmedetomidine group (group α2AAR-siRNA+D).H/R was produced by exposing cells to 1％ O2-5％ CO2-94％ N2 for 24 h followed by 4-h reoxygenation.Cells were incubated for 1 h with dexmedetomidine at the final concentration of 1 nmol/L,and then H/R model was established in group D.In group α2AAR-siRNA+D,cells were transfected with 50 nmol/L α2AAR-siRNA,48 h later dexmedetomidine at the final concentration of 1 nmol/L was added,cells were incubated for 1 h,and then H/R model was established.The cell viability was measured using CCK-8 method,cell apoptosis rate was determined by flow cytometry,and the expression of TLR4 and NF-κB was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group H/R (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group H/R,the cell viability was significantly increased,the apoptosis rate was decreased,and the expression of TLR4 and NF-κB was down-regulated in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group α2AAR-siRNA+D (P＞0.05).Compared with group D,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group α2AAR-siRNA+D (P＜0.05).Conclusion The mechanism by which dexmedetomidine inhibits TLR4/NF-κB signaling pathway activation may be related to activating α2AAR during H/R-caused injury to alveolar type Ⅱ epithelial cells.