猫眼草酚D抑制小鼠急性肺损伤的作用及其机制研究  

Study on the effect and mechanism of chrysosplenol D on inhibiting acute lung injury in mice

作　　者：张钦钦 曾梦楠[1,2,3] 张贝贝 吕雅鑫 曹兵 石静亚 郭彭莉 贾菊芳 刘萌 冯卫生 郑晓珂[1,2,3] ZHANG Qin-qin;ZENG Meng-nan;ZHANG Bei-bei;LV Ya-xin;CAO Bing;SHI Jing-ya;GUO Peng-li;JIA Ju-fang;LIU Meng;FENG Wei-sheng;ZHENG Xiao-ke(Henan University of Chinese Medicine,Zhengzhou 450046,China;The Enginand Technology Center for Chinese Medicine Development of Henan Province,Zhengzhou 450046,China;Collaborative Innovation Center far Chinese Medicine and Respiratory Diseases by Henan Province and Education Ministry of P.R.China,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,郑州450046 [2]河南省中药开发工程技术研究中心,郑州450046 [3]河南中医药大学,呼吸疾病中医药防治省部共建协同创新中心,郑州450046

出　　处：《中国新药杂志》2022年第4期362-368,共7页Chinese Journal of New Drugs

基　　金：河南省重大科技专项资助项目(171100310500);河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才资助项目(ZYQR 201810080)。

摘　　要：目的:探讨怀菊花茎叶中猫眼草酚D(chrysosplenol D,CD)对脂多糖(lipopolysaccharide, LPS)所致小鼠急性肺损伤(acute lung injury, ALI)的预防作用并初步探讨其作用机制。方法:用LPS诱导ALI模型,苏木素-伊红(HE)染色观察肺组织病理学变化;流式细胞术检测原代肺细胞凋亡和活性氧(reactive oxygen species, ROS)水平;酶法检测肺组织中谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)、超氧化物歧化酶(superoxide dismutase, SOD)、丙二醛(malondialdehyde, MDA)含量;ELISA法检测肺泡灌洗液中炎症因子白介素-6(interleukin-6,IL-6)、白介素-1β(interleukin-1β,IL-1β)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;Western blot法检测Toll样受体4(Toll like receptor 4,TLR4)-NOD样受体热蛋白结构域3(NOD-like receptor thermal protein domain 3,NLRP3)炎症小体通路相关蛋白。结果:在脂多糖诱导的急性肺损伤模型中,猫眼草酚D能使肺脏病理变化有所改善;原代肺细胞凋亡率和ROS水平降低;GSH-Px, SOD水平显著升高,MDA降低;IL-6,IL-1β和TNF-α水平显著降低;TLR4,NLRP3和髓样分化因子(myeloid differentiation factor 88,MyD88)及IL-1β蛋白水平降低。结论:怀菊花茎叶中猫眼草酚D可能通过调节TLR4-NLRP3通路降低炎症、氧化应激与凋亡水平从而改善脂多糖诱导的急性肺损伤。Objective: To investigate the preventive effect and mechanism of chrysosplenol D in the stems and leaves of Chrysanthemum morifolium Ramat on mice with acute lung injury(ALI) induced by lipopolysaccharide(LPS). Methods: ALI model was induced by LPS. The pathological changes of lung tissue were observed by hematoxylin-eosin(HE) staining. The levels of apoptosis and reactive oxygen species(ROS) in primary lung cells were detected by flow cytometry. Determination of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in lung tissue was performed by enzymatic method. The levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid were detected by ELISA. The proteins related to Toll like receptor 4-NOD-like receptor thermal protein domain 3(TLR4-NLRP3) pathway were detected by Western blot. Results: In the LPS-induced ALI model, chrysosplenol D could improve the pathological changes of the lung. The levels of apoptosis rate and ROS in primary lung cells decreased. The levels of GSH-Px and SOD increased significantly, while MDA decreased. The levels of IL-6, IL-1β and TNF-α decreased significantly. The protein levels of TLR4, NLRP3, myeloid differentiation factor 88(MyD88) and IL-1β decreased. Conclusion: Chrysoplenol D in the stems and leaves of Chrysanthemum morifolium Ramat may improve LPS-induced acute lung injury by reducing the levels of inflammation, oxidative stress and apoptosis through regulating TLR4-NLRP3 pathway.

关 键 词：猫眼草酚D 急性肺损伤 脂多糖 Toll样受体-NOD样受体热蛋白结构域3 

分 类 号：R965[医药卫生—药理学]