小白菊内酯通过介导miR-141-3p/PDCD4通路改善LPS诱导的急性肺损伤  

Parthenolide ameliorates LPS-induced acute lung injury by the miR-141-3p/PDCD4 axis

作　　者：张焕华 胡珊[2] 于丽丽[3] 丁明罡[1] 李芳 ZHANG Huan-hua;HU Shan;YU Li-li;DING Ming-gang;LI Fang(Emergency Department,Qingdao Traditional Chinese Medicine Hospital,Qingdao Haici Hospital,Qingdao 266033,China;Department of Nephrology,Qingdao Traditional Chinese Medicine Hospital,Qingdao Haici Hospital,Qingdao 266033,China;Department of Neurology,Qingdao Traditional Chinese Medicine Hospital,Qingdao Haici Hospital,Qingdao 266033,China)

机构地区：[1]青岛市中医医院,青岛市海慈医院急诊科,青岛266033 [2]青岛市中医医院,青岛市海慈医院肾内科,青岛266033 [3]青岛市中医医院,青岛市海慈医院神经内科,青岛266033

出　　处：《现代免疫学》2024年第4期323-331,共9页Current Immunology

基　　金：山东省中医药科技发展计划项目(2015-353)。

摘　　要：为探讨小白菊内酯(parthenolide,PTL)对LPS诱导的急性肺损伤(acute lung injury,ALI)的作用及其调控机制,给予C57BL/6小鼠单次气管内给药LPS(4 mg/kg)构建ALI小鼠模型,MLE-12细胞与1μg/mL LPS孵育体外诱导细胞损伤。小鼠被随机分为4组:对照组、 LPS组、 LPS+5 mg/kg PTL组和LPS+10 mg/kg PTL组,每组10只。采用H-E染色观察肺组织病理学变化;收集肺组织测定肺组织湿重(wet weight,W)/干重(dry weight,D)比值;ELISA测定小鼠支气管肺泡灌洗液和细胞中TNF-α、 IL-1β、 IL-6水平。miR-141-3p和程序性细胞死亡因子4(programmed cell death 4,PDCD4)水平分别通过qRT-PCR和Western blotting检测;细胞活力和凋亡分别通过CCK-8法和FACS检测。结果显示,与对照组比较,LPS组小鼠肺组织W/D比值及TNF-α、 IL-1β、 IL-6、 PDCD4水平升高(P<0.05),肺泡壁增厚,肺间质弥漫性出血和炎症浸润增加,肺组织病理评分升高(P<0.05),miR-141-3p表达降低(P<0.05);与LPS组比较,LPS+5 mg/kg PTL组和LPS+10 mg/kg PTL组W/D比值及TNF-α、 IL-1β、 IL-6、 PDCD4水平降低(P<0.05),肺泡壁增厚减轻,肺间质弥漫性出血和炎症细胞浸润减少,肺组织病理评分降低(P<0.05),miR-141-3p表达增加(P<0.05),且呈剂量依赖性;与对照组比较,LPS组细胞活力和miR-141-3p表达降低(P<0.05),细胞凋亡率及TNF-α、 IL-1β、 IL-6、 PDCD4水平升高(P<0.05);与LPS组比较,5和10μmol/L PTL处理后,细胞活力及miR-141-3p表达增加(P<0.05),细胞凋亡率及TNF-α、 IL-1β、 IL-6、 PDCD4水平降低(P<0.05),且呈剂量依赖性;此外,PDCD4被确定与miR-141-3p靶向结合。该研究提示,PTL可以通过调节miR-141-3p/PDCD4通路抑制炎症以缓解LPS诱导的ALI。This study aims to explore the effects and regulatory mechanism of parthenolide(PTL) on LPS-induced acute lung injury(ALI).C57BL/6 mice were used to establish the ALI model by a single intratracheal administration of LPS(4 mg/kg).For in vitro LPS-induced cell injury,MLE-12 cells were treated with 1 μg/mL LPS.Mice were randomly divided into four groups:control group,LPS group,LPS+5 mg/kg PTL doses group,and LPS+10 mg/kg PTL doses group,with 10 mice in each group.H-E staining was used to examine the pathological changes of lung tissue.Lung tissues were collected and the ratio of wet weight(W)to dry weight(D) was measured.IL-1β,IL-6,and TNF-α content in alveolar lavage fluid and cells was measured by ELISA.The levels of miR-141-3p and programmed cell death 4(PDCD4)were measured by qRT-PCR and Western blotting,respectively.Cell viability and apoptosis were determined by CCK-8 method and FACS,respectively.The results showed that compared to those of the control group,the lung tissue W/D ratio,TNF-α,IL-1β,IL-6,and PDCD4 expression levels were significantly increased(P<0.05).Alveolar wall thickening,diffuse pulmonary interstitial hemorrhage,and inflammatory infiltration were increased and the pathological score of lung tissue was also increased(P<0.05),while the expression of miR-141-3p was decreased in the LPS group(P<0.05).Compared to those of the LPS group,the W/D ratio,TNF-α,IL-1β,IL-6,and PDCD4 levels were decreased(P<0.05),alveolar wall thickening was alleviated,diffuse pulmonary interstitial hemorrhage and inflammatory infiltration were reduced,pathological scores of lung tissue were decreased(P<0.05),and the expression of miR-141-3p was increased in LPS+5 mg/kg PTL doses group and LPS+10 mg/kg PTL doses group(P<0.05) in a dose-dependent manner.Compared to those of the control group,the cell viability and miR-141-3p expression were decreased(P<0.05),while the apoptosis rate and the levels of TNF-α,IL-1β,IL-6,and PDCD4 were increased in the LPS group(P<0.05).The cell viability and miR-141-3p expression we

关 键 词：急性肺损伤 小白菊内酯 微小RNA-141-3p 程序性细胞死亡因子4 

分 类 号：R285.5[医药卫生—中药学]