芒柄花素对脂多糖诱导的肺泡上皮细胞凋亡及炎症反应的抑制作用  

Inhibitory effects of formononetin on lipopolysaccharide-induced apoptosis and inflammatory response in alveolar epithelial cells

作　　者：林海 易金容 饶运帷 LIN Hai;YI Jinrong;RAO Yunwei(Dept.of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Gannan Medical College,Jiangxi Ganzhou 341000,China;Dept.of Anesthesiology,Ganzhou Maternal and Child Health Hospital,Jiangxi Ganzhou 341000,China)

机构地区：[1]赣南医学院第一附属医院呼吸与危重医学科,江西赣州341000 [2]赣州市妇幼保健院麻醉科,江西赣州341000

出　　处：《中国药房》2023年第22期2721-2726,共6页China Pharmacy

基　　金：江西省省级科技计划项目(No.20192BAB205009);江西省卫生健康委科技计划项目(No.202130701)。

摘　　要：目的 基于磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路,探讨芒柄花素对脂多糖(LPS)诱导的肺泡上皮细胞凋亡及炎症反应的抑制作用。方法 体外培养肺癌人肺泡基底上皮细胞A549,分为对照组(不干预)、模型组(1μg/mL LPS)、芒柄花素不同浓度组(1μg/mL LPS+6.25、12.5、25、50μmol/L芒柄花素),检测各组细胞培养液中炎症因子(白细胞介素8、肿瘤坏死因子α)水平和细胞活力。另取A549细胞分为对照组、模型组(1μg/mL LPS)、LPS+25组(1μg/mL LPS+25μmol/L芒柄花素)、抑制剂组(1μg/mL LPS+20μmol/L LY294002)、芒柄花素+抑制剂组(1μg/mL LPS+25μmol/L芒柄花素+20μmol/L LY294002)和芒柄花素+激活剂组(1μg/mL LPS+25μmol/L芒柄花素+10μmol/L SC79),检测各组细胞炎症因子分泌水平和mRNA表达水平、细胞凋亡情况和PI3K/Akt信号通路关键蛋白表达情况。结果 与模型组比较,25μmol/L的芒柄花素能显著降低细胞培养液中炎症因子水平,显著升高细胞活力(P<0.05)。与对照组比较,模型组细胞中炎症因子的分泌水平和mRNA表达水平,细胞凋亡率,磷酸化Akt、磷酸化PI3K蛋白的相对表达量均显著升高(P<0.05);与模型组比较,LPS+25组和抑制剂组细胞上述指标均显著降低(P<0.05);与LPS+25组比较,芒柄花素+抑制剂组细胞上述指标均进一步降低,而芒柄花素+激活剂组细胞上述指标则显著升高(P<0.05)。结论 芒柄花素能够抑制LPS诱导的肺泡上皮细胞凋亡并改善其炎症反应,上述作用与抑制PI3K/Akt信号通路有关。OBJECTIVE To investigate the inhibitory effects of formononetin on lipopolysaccharide(LPS)-induced apoptosis and inflammatory response in alveolar epithelial cells through phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.METHODS Human lung cancer alveolar basal epithelial cells A549 were cultured in vitro and divided into control group(no intervention),model group(1μg/mL LPS),different concentrations of formononetin groups(1μg/mL LPS+6.25,12.5,25,50μmol/L formononetin).The levels of inflammatory factors(interleukin-8,tumor necrosis factor-α)and cell viability were detected in each group.Another A549 cells were divided into control group,model group(1μg/mL LPS),LPS+25 group(1μg/mL LPS+25μmol/L formononetin),inhibitor group(1μg/mL LPS+20μmol/L LY294002),formononetin+inhibitor group(1μg/mL LPS+25μmol/L formononetin+20μmol/L LY294002)and formononetin+activator group(1μg/mL LPS+25μmol/L formononetin+10μmol/L SC79).The secretion levels and mRNA expressions of inflammatory factors,cell apoptosis,and expressions of the key proteins of PI3K/Akt signaling pathway were detected in each group.RESULTS Compared with model group,the levels of inflammatory factors were decreased significantly after the intervention of 25μmol/L of formononetin,and the cell viability was increased significantly(P<0.05).Compared with the control group,the secretion levels and mRNA expressions of inflammatory factors,apoptotic rate,and relative expressions of phosphorylated Akt and phosphorylated PI3K of the model group were increased significantly(P<0.05).Compared with the model group,the above indexes of the LPS+25 group and the inhibitor group were decreased significantly(P<0.05).Compared with the LPS+25 group,the above indicators of formononetin+inhibitor group were further decreased,while those of formononetin+activator group were increased significantly(P<0.05).CONCLUSIONS Formononetin can inhibit LPS-induced epithelial cell apoptosis and improve inflammatory response,and the mechanism may be related to th

关 键 词：芒柄花素 肺泡上皮细胞 脂多糖 磷脂酰肌醇3激酶/蛋白激酶B信号通路 凋亡 炎症反应 

分 类 号：R965[医药卫生—药理学]