木犀草素对体外循环导致急性肺损伤的保护作用及其机制研究  

Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism

作　　者：凌云飞[1] 李田歌 曹嵘 钱永军[1] LING Yunfei;LI Tiange;CAO Rong;QIAN Yongjun(Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu,610041,P.R.China)

机构地区：[1]四川大学华西医院心脏大血管外科,成都610041

出　　处：《中国胸心血管外科临床杂志》2023年第8期1181-1187,共7页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：四川省干部保健科研课题(川干研2023-116);成都市科技局技术创新研发项目(2019-YF05-00183-SN)。

摘　　要：目的探讨雾化吸入纳米木犀草素制剂对体外循环导致急性肺损伤的保护作用,初步探究木犀草素的抗炎机制,为临床应用提供基础研究依据。方法采用随机数字表法将30只雄性SD大鼠(5~6周龄,体重160~190 g)分为术前基线(BL)组、动静脉部分转流(ECC)组、木犀草素雾化给药预处理1 h组、2 h组、3 h组,每组6只。BL组不予任何处理,直接采集肺组织标本;ECC组行机械通气,颈动静脉插管后全身肝素化,转流30 min,观察60 min,采集肺组织标本;1 h、2 h、3 h组分别于转流前1 h、2 h、3 h将实验对象置于小动物雾化给药仪雾化给药木犀草素纳米制剂,后续操作同ECC组。检测肺组织炎性水平,评估肺组织病理损伤程度,使用蛋白免疫印迹法(WB)检测各组肺组织样本细胞质中p65、IκB激酶(IKK)α、IKKβ、IKKγ的含量。结果肺组织炎性水平检测和病理损伤程度评估显示,与ECC组相比,木犀草素雾化给药1 h、2 h、3 h组肺组织白细胞介素6、肿瘤坏死因子-α水平和病理损伤程度均下降,3 h组最明显,与ECC组差异有统计学意义(P<0.05)。WB检测显示,与ECC组相比,木犀草素雾化给药1 h、2 h、3 h组肺组织p65水平下降;IKKβ水平升高,3 h组最显著,与ECC组差异有统计学意义(P<0.05)。结论木犀草素在ECC导致的急性肺损伤中具有保护作用,提前3 h雾化的肺保护作用最佳。其机制可能是通过抑制IKKβ磷酸化过程,从而抑制核因子κB(NF-κB)经典信号通路,发挥保护ECC导致的急性肺损伤的作用。Objective To investigate the protective effect of atomized inhalation of nano-luteolin preparation on acute lung injury caused by extracorporeal circulation,and to explore the anti-inflammatory mechanism of luteolin,so as to provide study basis for clinical application.Methods Thirty male SD rats aged 5-6 weeks and weighting 160-190 g,were randomly divided into a preoperative baseline(BL)group,arteriovenous partial diversion(ECC)group,luteolin atomization pretreatment for 1 h group,2 h group,and 3 h group by random number method,with 6 rats in each group.In the BL group,lung tissue samples were collected directly without any treatment.The ECC group received mechanical ventilation,and the whole body was heparinized after the jugular arteriovenous intubation.The flow was transferred for30 minutes,followed by observation for 60 minutes,then lung tissue samples were collected.Subjects in the 1 h,2 h and 3 h groups were placed in a small animal atomizer 1 h,2 h and 3 h before flow transfer respectively,and the subsequent operation was the same as that in the ECC group.The inflammatory level of lung tissue was detected to evaluate the degree of pathological injury of lung tissue.Western blotting(WB)was used to detect the contents of p65,IKKα,IKKβand IKKγin the cytoplasm of lung tissue samples of each group.Results Compared with the ECC group,the levels of IL-6 and TNF-αin lung tissues and the degree of pathological injury in the 1 h,2 h and 3 h groups decreased,and the difference between the 3 h group and the ECC group was statistically different(P<0.05).WB results showed that compared with the ECC group,the levels of p65 in lung tissue of the 1 h,2 h and 3 h groups decreased;the levels of IKKβin the lung tissue increased in the 1 h,2 h and 3 h groups,and the difference of the 3 h group was statistically different from the ECC group(P<0.05).Conclusion Luteolin has a protective effect on acute lung injury induced by ECC,and atomization 3 h in advance has the best protective effect on lung.The mechanism plays a prot

关 键 词：体外循环 急性肺损伤 木犀草素 核因子ΚB IΚB激酶 

分 类 号：R285.5[医药卫生—中药学]