沉默信息调节因子1调控小窝蛋白-1对大鼠急性肺损伤的影响OACSTPCD

Objective To investigate the effect of silence infor-mation regulator 1(SIRT1)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)rats via regulating caveolin-1(Cav-1).Methods Forty male Sprague-Dawley rats were divided into 4 groups:normal saline group(group NS),LPS group(group L),LPS+SIRT1 activator SRT1720-pretreated group(group S),and LPS+SIRT1 inhibitor EX527-pretreated group(group E),10 in each group.The animals in groups S and E received intravenous injections of 10 mg/kg of SRT1720 and 1 μg/kg of EX527,respectively in the tail.After 30 mintues,the animals in groups L,S,and E were intranasally dripped with 5 mg/kg of LPS(diluted to 0.5 mL with 0.9％normal saline)to establish the ALI models.The animals in group NS received the same amount of 0.9％normal saline.All rats were sacrificed by carotid bloodletting six hours after subjection to LPS.Lung tissue was taken to observe its injury under a light microscope(by using Smith score),the IL-6,TNF-α level,and myeloperoxidase(MPO)activity of lung tissues were detected by ELISA method,and wet-dry ratio(W/D)was calculated.The expression levels of SIRT1,Cav-1 and Toll-like receptor 4(TLR4)in lung tissues were determined by immunohistochemistry,and the mRNA expression levels of SIRT1,Cav-1 and TLR4 were determined by RT-qPCR.Results Compared with the group NS,the Smith score,IL-6 and TNF-α expressions,MPO activity,and W/D ratio were increased after LPS injection in groups L,S and E;the TLR4 expression was up-regulated,while the SIRT1 and Cav-1 expressions were down-regulated(all P＜0.05).Compared with the group L,the Smith score and IL-6,TNF-α were decreased in group S;the TLR4 expression was down-regulated,while the SIRT1 and Cav-1 expressions were up-regulated(all P＜0.05).Compared with group L,the Smith score,IL-6 and TNF-α expressions,MPO activity and W/D ratio in group E were increased after LPS injection,the SIRT1 and Cav-1 expressions were down-regulated,and the TLR4 expression was up-regulated(all P＜0.05).Compared with the group S,the Smith score,IL-6 and TNF-α expressions,MPO activity and W/D ratio in group E were increased after LPS injection,the SIRT1 and Cav-1 expressions were down-regulated,and the TLR4 expression was up-regulated(all P＜0.05).Conclusion SIRT1 may alleviate the severity of LPS-induced ALI by activating the expression of Cav-1.