苍术酮通过调节Nrf2-NLRP3通路减轻LPS诱导的小鼠急性肺损伤实验研究  

Benefits of Atractylon via Nrf2-NLRP3 Signaling Pathway Modulation on Mice with LPS-induced Acute Lung Injury

作　　者：陈天阳[1] 李鹏程 严佳 郑佳萍 金源源 成扬[1] 王倩[1] Chen Tianyang;Li Pengcheng;Yan Jia;Zheng Jiaping;Jin Yuanyuan;Cheng Yang;Wang Qian(Shuguang Hospital Afiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海210203

出　　处：《中国中医急症》2024年第2期219-222,226,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82074156);上海中医药大学预算内项目(2021LK074)。

摘　　要：目的研究苍术酮调节核因子NF-E2相关因子(Nrf2)-NLRP3通路对LPS诱导急性肺损伤(ALI)小鼠的保护作用。方法构建ALI小鼠模型,实验分为对照组、模型组、地塞米松组及苍术酮低、中、高剂量组。ELISA测定各组小鼠血清及肺泡灌洗液中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平;通过测定肺组织湿/干质量比重(W/D),评估其水肿程度,检测肺组织抗髓过氧化物酶抗体(MPO)、谷胱甘肽过氧化物酶(GSH-Px)超氧化物歧化酶(SOD)及丙二酮(MDA)含量以评估其体内抗氧化损伤的作用;HE染色法检查肺损伤情况,并进行评分;RT-qPCR测定各组小鼠肺组织Nrf2、HO-1、NLRP3、ASC、Caspase-1、IL-1β、IL-18mRNA水平。结果苍术酮对LPS诱导的小鼠ALI具有较好的保护作用,可降低小鼠血清及肺泡灌洗液中TNF-α、IL-1β、IL-6水平和W/D比值、肺组织MPO、MDA及NLRP3、ASC、Caspase-1、IL-1β、IL-18mRNA水平,提高血清IL-10水平及肺组织GSH-Px、SOD及Nrf2、HO-1 mRNA水平,明显改善肺组织学病理表现,降低肺组织病理评分,且呈剂量依赖性(P<0.05)。结论苍术酮可通过调节炎症因子及氧化应激以缓解ALI小鼠肺损伤,其机制可能与调节Nrf2-NLRP3通路有关。Objective:To investigate the protective effect of atractylon on LPS-induced acute lung injury(ALI)in mice by regulating Nrf2-NLRP3 signaling pathway.Methods:A mouse model of ALI was established.The mice were divided into the control group,model group,dexamethasone group,and atractylon low,middle,high dose group.The levels of TNF-α,IL-1β,IL-6 and IL-10 in serum and bronchoalveolar lavage fluid(BALF)were measured by ELISA.The wet/dry weight ratio(W/D)of lung tissue was measured to evaluate the degree of edema.The activities of MPO,GSH-Px,SOD and MDA in lung tissue were detected to evaluate the anti-oxidative damage in vivo.The lung injury was evaluated by HE staining and scored.RT-qPCR was used to measure the mRNA levels of Nrf2,HO-1,NLRP3,ASC,caspase-1,IL-1β,and IL-18 in lung tissue of mice in each group.Results:Atractylon showed a good protective effect on LPS-induced ALI in mice,which reduced the levels of TNF-α,IL 1β,IL-6 and W/D ratio in serum and alveolar lavage fluid,MPO,MDA in lung tissue and the mRNA levels of NL-RP3,ASC,caspase-1,IL-1β,IL-18;increased the level of IL-10 in serum and the levels of GSH-Px,SOD in lung tissue,the mRNA levels of Nrf2 and HO-1;the pathological manifestations of lung tissue were improved,and the pathological scores of lung tissue were decreased in a dose-dependent manner.Conclusion:Atractylon can al-leviate lung injury in ALI mice by regulating inflammatory factors and oxidative stress,which may be related to the regulation of Nrf2-NLRP3 pathway.

关 键 词：急性肺损伤 苍术酮 NRF2 NLRP3 小鼠 

分 类 号：R285.5[医药卫生—中药学]