阿托伐他汀钙通过上调SIRT1/NF-κB信号通路促进慢性阻塞性肺疾病大鼠肺组织损伤恢复  

Atorvastatin calcium promotes the recovery of lung tissue injury in rats with chronic obstructive pulmonary disease by up-regulating the SIRT1/NF-κB signaling pathway

作　　者：李蔚[1] 安兴 刘磊 LI Wei;AN Xing;LIU Lei(Department of Respiratory and Critical Care Medicine,Chongqing Hospital of Traditional Chinese Medicine&First Affiliated Hospital of Chinese Medicine College,Chongqing 400020,China)

机构地区：[1]重庆市中医院(中医药学院附属第一医院)呼吸与危重症医学科,400020

出　　处：《免疫学杂志》2024年第11期824-830,共7页Immunological Journal

摘　　要：目的探讨阿托伐他汀钙(ATR)调节沉默信息调节因子1(SIRT1)/核因子κB(NF-κB)信号通路对慢性阻塞性肺疾病(COPD)大鼠肺组织损伤的影响。方法脂多糖气管注射联合烟熏建立COPD大鼠,并以仅注射生理盐水的大鼠为对照组,将COPD大鼠随机分为COPD组、ATR(5 mg/kg)组、阳性药(0.2 mg/kg地塞米松)组、EX527(5 mg/kg EX527)组、ATR+EX527组,干预结束后,检测大鼠第1秒用力呼气容积/用力肺活量(FEV1/FVC)、呼气峰流量(PEF);腹主动脉采集血样,检测上清液中肿瘤坏死因子(TNF)-α,白细胞介素(IL)-6,IL-1β水平;分离肺组织,检测超氧化物歧化酶(SOD)和丙二醛(MDA)水平及病理变化,并依据组织损伤程度进行评分;同时检测SIRT1、NF-κB p65 mRNA及蛋白表达。结果COPD组TNF-α、IL-1β、IL-6水平、MDA水平、病理评分、NF-κB p65 mRNA、p-NF-κB p65/NF-κB p65表达高于对照组,但FEV1/FVC、PEF、SOD水平、SIRT1 mRNA及蛋白表达低于对照组(P<0.05);ATR组、阳性药组TNF-α、IL-1β、IL-6水平、MDA水平、病理评分、NF-κB p65 mRNA、p-NF-κB p65/NF-κB p65表达低于COPD组,但FEV1/FVC、PEF、SOD水平、SIRT1 mRNA及蛋白表达高于COPD组(P<0.05);EX527组TNF-α、IL-1β、IL-6水平、MDA水平、病理评分、NF-κB p65 mRNA、p-NF-κB p65/NF-κB p65表达高于COPD组,但FEV1/FVC、PEF、SOD水平、SIRT1 mRNA及蛋白表达低于COPD组(P<0.05);ATR+EX527组TNF-α、IL-1β、IL-6水平、MDA水平、病理评分、NF-κB p65 mRNA、p-NF-κB p65/NF-κB p65表达高于ATR组,但低于EX527组(P<0.05),ATR+EX527组FEV1/FVC、PEF、SOD水平、SIRT1 mRNA及蛋白表达低于ATR组,但高于EX527组(P<0.05)。结论ATR通过上调SIRT1表达抑制NF-κB表达,减轻COPD大鼠肺组织损伤。Objective To investigate the effect of atorvastatin calcium(ATR)on lung tissue injury in rats with chronic obstructive pulmonary disease(COPD)by regulating the sirtuin type 1(SIRT1)/NF-κB signaling pathway.Methods COPD rats were established by tracheal injection of lipopolysaccharide combined with smoking,and rats injected with physiological saline alone were used as the control group.COPD rats were randomly assigned into COPD group,ATR(5 mg/kg)group,positive drug(0.2 mg/kg dexamethasone)group,inhibitor(5 mg/kg EX527)group,and ATR+inhibitor group.After the intervention,the forced expiratory volume in the first second/forced vital capacity(FEV1/FVC)and peak expiratory flow(PEF)of the rats were measured.Blood samples were collected from the abdominal aorta,and the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1βin the supernatant were detected;the lung tissue was isolated,and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA),and pathological changes were detected and the degree of tissue damage were scored.Meanwhile,the expression of SIRT1 and NF-κB p65 mRNA and protein were detected.Results The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the COPD group were higher than those in the control group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein were lower than those in the control group(P<0.05).The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the ATR group and positive drug group were lower than those in the COPD group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein were higher than those in the COPD group(P<0.05).The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the inhibitor group were higher than those in the COPD group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA

关 键 词：阿托伐他汀钙 慢性阻塞性肺疾病 肺组织 SIRT1/NF-κB信号通路 

分 类 号：R285.5[医药卫生—中药学]