鸢尾素通过Nrf2/GPX4信号通路减轻脂多糖诱导的大鼠急性肺损伤的作用机制  

The mechanism of irisin via Nrf2/GPX4 signaling pathway in alleviating lipopolysaccharide-induced acute lung injury in rats

作　　者：罗晶[1] 彭君[1] 张静[1] 王赟[1] 李心怡[1] Jing LUO#;Jun PENG#;Jing ZHANG;Yun WANG;Xin-Yi LI(Department of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,武汉430071

出　　处：《医学新知》2023年第2期83-90,共8页New Medicine

基　　金：国家自然科学基金青年科学基金项目(82002033)。

摘　　要：目的探讨Nrf2/GPX4信号通路在鸢尾素减轻脂多糖(LPS)诱导的大鼠急性肺损伤中的作用。方法将72只健康雄性SD大鼠随机分为对照组(C组)、急性肺损伤组(ALI组)、鸢尾素组(Ir组)、鸢尾素+Nrf2抑制剂组(Ir+ML385组)。各组于模型制备后24 h收集支气管肺泡灌洗液(BALF),测定BALF中蛋白浓度,采用ELISA法检测BALF中IL-6、TNF-α含量;HE染色观察肺组织病理学结果并评分,计算肺组织湿/干重比;比色法检测肺组织中Fe^(2+)、MDA、GSH含量;Western blot测定肺组织中GPX4、ACSL4及胞核Nrf2的表达。结果与C组比较,ALI组中BALF蛋白浓度、IL-6、TNF-α含量、肺组织病理损伤评分、湿/干重比、Fe^(2+)、MDA含量均增加,GSH含量降低,GPX4表达降低,ACSL4、胞核Nrf2表达增加(P<0.05);与ALI组比较,Ir组中BALF蛋白浓度、IL-6、TNF-α含量、肺组织病理损伤评分、湿/干重比、Fe^(2+)、MDA含量均降低,GSH含量增加,GPX4、胞核Nrf2表达增加,ACSL4表达降低(P<0.05);与Ir组比较,Ir+ML385组中BALF蛋白、IL-6、TNF-α含量、肺组织病理损伤评分、湿/干重比、Fe^(2+)、MDA含量均增加,GSH含量降低,GPX4、胞核Nrf2表达降低,ACSL4表达增加(P<0.05)。结论Nrf2/GPX4信号通路参与了鸢尾素减轻LPS诱导的大鼠急性肺损伤的过程,其与抑制铁死亡有关。Objective To study the role of Nrf2/GPX4 signaling pathway in irisin alleviating lipopolysaccharide(LPS)-induced acute lung injury in rats.Method Seventy-two healthy male SD rats were randomly divided into control group(C group),acute lung injury group(ALI group),irisin group(Ir group),irisin+Nrf2 inhibitor group(Ir+ML385 group).24 hours after the model preparation,bronchoalveolar lavage fluid(BALF)was collected for protein concentration determination,and the contents of IL-6 and TNF-αin BALF were detected by ELISA.Pathologic results of lung tissue sections were observed by HE staining and scored,and the wet/dry weight ratio of the lung tissue was calculated.The contents of Fe^(2+),MDA and GSH in lung tissue homogenate were detected by colorimetric method.The protein levels of GPX4,ACSL4 and nuclear Nrf2 in lung tissues were determined by western blot(WB).Result Compared with the control group,the protein contents in BALF,the IL-6 and TNF-αcontents,lung pathological injury score,wet/dry weight ratio,the contents of Fe^(2+)and MDA were increased,the GSH content and GPX4 level were decreased,the protein levels of ACSL4 and nuclear Nrf2 were increased in ALI group(P<0.05).Compared with the ALI group,the protein contents in BALF,the IL-6 and TNF-αcontents,lung pathological injury score,wet/dry weight ratio,Fe^(2+)and MDA contents were decreased,the GSH content as well as the protein levels of GPX4 and nuclear Nrf2 were increased,ACSL4 level was decreased in Ir group(P<0.05).Compared with the Ir group,the protein contents in BALF,the IL-6 and TNF-αcontents,lung pathological injury score,wet/dry weight ratio,Fe^(2+)and MDA contents were increased,the GSH content as well as the protein levels of GPX4 and nuclear Nrf2 were decreased,ACSL4 level was increased in the Ir+ML385 group(P<0.05).Conclusion Nrf2/GPX4 signaling pathway is involved in irisin alleviating LPS-induced acute lung injury in rats,which is associated with the inhibition of ferroptosis.

关 键 词：鸢尾素 急性肺损伤 核因子E2相关因子2 谷胱甘肽过氧化物酶4 铁死亡 

分 类 号：R285.5[医药卫生—中药学]