摘要
目的探讨依托咪酯对脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)的影响。方法将小鼠随机分为对照组、模型组(气管滴注LPS 10 mg/kg建立ALI小鼠模型)、依托咪酯低(5.0 mg/kg)、中(10.0 mg/kg)和高剂量(20.0 mg/kg)干预组、阳性对照(血必净注射液,100μL)组,每组15只。12 h后,用Buxco肺功能仪检测小鼠呼吸功能指标-肺顺应性、呼吸频率、气道阻力;ELISA测定小鼠血清中炎性因子TNF-α和IL-6含量;计算小鼠肺脏湿重/干重(W/D)比值;HE染色观察肺组织病理学;Western blot检验肺组织中TXNIP、NLRP3蛋白表达。另在20.0 mg/kg依托咪酯的基础上加入TXNIP过表达载体(pcDNA3.1-TXNIP,5 nmol/L)并设置阴性对照组(pcDNA3.1),探究依托咪酯调控TXNIP/NLRP3信号通路对LPS诱导的ALI的影响。结果与对照组相比,模型组小鼠肺组织出现炎性细胞浸润、肺泡壁增厚现象,肺顺应性、呼吸频率显著降低(P<0.05),肺组织病理评分、气道阻力、血清TNF-α和IL-6含量、肺脏W/D比值、肺组织TXNIP、NLRP3蛋白表达均显著增加(P<0.05);与模型组相比,依托咪酯低、中、高剂量组小鼠肺组织炎性细胞浸润、肺泡壁增厚得到不同程度的缓解,肺顺应性、呼吸频率逐渐增加(P<0.05),肺组织病理评分、气道阻力、血清TNF-α和IL-6含量、肺脏W/D比值、肺组织TXNIP、NLRP3蛋白表达逐渐降低(P<0.05)。与pcDNA3.1组相比,pcDNA3.1-TXNIP组可逆转依托咪酯对小鼠的保护作用。结论依托咪酯可以抑制炎性反应,改善肺组织病理损伤。
Objective To investigate the effect of etomidate on acute lung injury(ALI)induced by lipopolysaccharide(LPS)in mice.Methods The mice were randomly divided into control group,model group,etomidate groups of low(5.0 mg/kg),medium(10.0 mg/kg)and high dose(20.0 mg/kg)and positive control(Xuebijing injection,100μL)group with 15 mice in each.After 12 hours,the Buxco pulmonary function meter was used to detect the mouse respiratory function indicators-lung compliance,respiratory frequency,airway resistance;ELISA method was used to determine the contents of inflammatory factors-tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the serum of mice;the wet weight/dry weight(W/D)ratio of the mouse lungs was calculated;HE staining microscopy was used to observe the pathological changes of lung tissue in mice;Western blot was used to test the expression of TXNIP and NLRP3 proteins in mouse lung tissue.In addition,TXNIP over-expression vector(PCDNA3.1-TXNIP,5 nmol/L)was added on the basis of 20.0 mg/kg etomidate and negative control group(pcDNA3.1)was set to explore the effect of etomidate regulation through TXNIP/NLRP3 signaling pathway on LPS-induced ALI.Results Compared with the control group,the lung tissue of the model group showed inflammatory cell infiltration and alveolar wall thickening,the lung compliance and respiratory frequency were significantly reduced(P<0.05).The lung tissue pathology score,airway resistance,serum content of TNF-αand IL-6,lung W/D ratio,lung tissue TXNIP,NLRP3 protein expression were all increased significantly(P<0.05).Compared with the model group,the inflammatory cell infiltration and alveolar wall thickening of the lung tissue of the mice in the etomidate low,medium and high dose groups were relieved to varying degrees and the lung compliance and respiratory frequency were gradually increased(P<0.05).The lung tissue pathology score,airway resistance,serum TNF-αand IL-6 contents,lung W/D ratio,lung tissue TXNIP,NLRP3 protein expression were gradually decreased(P<0.05).Compared with pcDNA3.1 group,pcDNA3.1-TXNIP group reversed protective effect of etomidate on mice.Conclusions Etomidate inhibits inflammatory response and improves pathological damage of lung tissue.
作者
景建闯
张志军
JING Jian-chuang;ZHANG Zhi-jun(Department of Anesthesiology,Anyang People's Hospital,Anyang 455000,China)
出处
《基础医学与临床》
2022年第12期1823-1828,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(8210151653)。
