Effect of silence infor-mation regulator 1 on lipopolysaccharide-induced acute lung injury rats via regulating caveolin-1
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.