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  

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

作　　者：费国方 刘静 童飞[2] 黄新华 FEI Guofang;LIU Jing;TONG Fei;HUANG Xinhua(Department of Anesthesiology,Huzhou Maternality and Child Health Care Hospital,Huzhou 313000,China)

机构地区：[1]湖州市妇幼保健院麻醉科,313000 [2]湖州市中心医院麻醉科

出　　处：《浙江医学》2024年第13期1357-1361,1386,I0003,共7页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2023KY315);湖州市应急科技计划项目(2020GZT02)。

摘　　要：目的探讨沉默信息调节因子1(SIRT1)调控小窝蛋白-1(Cav-1)对脂多糖(LPS)所致大鼠急性肺损伤(ALI)的影响。方法采用随机数字表法将40只SD大鼠分为对照组(NS组)、LPS组(L组)、LPS+SIRT1激动剂SRT1720组(S组)和LPS+SIRT1抑制剂EX527组(E组),每组各10只。S组和E组大鼠分别尾静脉注射SRT172010 mg/kg、EX5271μg/kg,30 min后L组、S组和E组滴鼻LPS 5 mg/kg(用0.9%氯化钠注射液稀释至0.5 mL)制备ALI模型,NS组滴鼻等量0.9%氯化钠注射液。6 h后颈动脉放血处死大鼠,取肺组织并在光镜下观察肺组织损伤情况(采用Smith评分评估),采用ELISA法检测肺组织IL-6、TNF-α水平和髓过氧化物酶(MPO)活性,计算肺组织湿重/干重(W/D)值。采用免疫组化法测定肺组织SIRT1、Cav-1、Toll样受体4(TLR4)蛋白表达水平,采用实时荧光定量PCR法检测肺组织SIRT1、Cav-1、TLR4 mRNA表达水平。结果与NS组比较,L组、S组和E组Smith评分、IL-6、TNF-α水平、MPO活性及W/D值升高,SIRT1、Cav-1表达下调,TLR4表达上调(均P<0.05)。与L组比较,S组Smith评分及IL-6、TNF-α水平降低,SIRT1、Cav-1表达上调,TLR4表达下调(均P<0.05);E组Smith评分、IL-6、TNF-α水平、MPO活性及W/D值升高,SIRT1、Cav-1表达下调,TLR4表达上调(均P<0.05)。与S组比较,E组Smith评分、IL-6、TNF-α水平、MPO活性及W/D值升高,SIRT1、Cav-1表达下调,TLR4表达上调(均P<0.05)。结论SIRT1通过上调Cav-1的表达减轻LPS所致大鼠ALI的严重程度。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 1μg/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-αlevel,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-αexpressions,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-αwere decreased in group S;the TLR4 expression was down-regulated,while the SIRT1 and Cav-1 expressions were upregulated(all P<0.05).Compared with group L,the Smith score,IL-6 and TNF-αexpressions,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 TN

关 键 词：沉默信息调节因子1 小窝蛋白-1 TOLL样受体4 脂多糖 急性肺损伤 

分 类 号：R563.8[医药卫生—呼吸系统]