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泽漆醇提物对LPS诱导小鼠急性肺损伤及其炎症信号通路MAPK/NF-κB的影响 被引量:17

Effect of Euphorbia helioscopia Alcohol Extract on MAPK/NF-κB Inflammation Pathway on Mice with Acute Lung Injury Induced by LPS
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摘要 目的:研究泽漆醇提物对脂多糖(LPS)所致急性肺损伤小鼠的保护作用并探讨其可能的作用机制。方法:50只雄性BALB/c小鼠按体质量随机分为正常组,模型组,地塞米松组(1.5 mg·kg^-1)及泽漆醇提物高、低剂量组(7.5,3.75 g·kg^-1)。除正常组外,其余各组采用鼻腔内滴入LPS建立小鼠急性肺损伤模型。利用全自动血液分析仪以及瑞氏-姬姆萨复合染色法检测并观察支气管肺泡灌洗液(BALF)中炎性细胞种类及数量;苏木素-伊红(HE)染色观察肺组织损伤情况;流式细胞仪检测BALF中炎性因子如肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6)的含量;蛋白免疫印迹法(Western blot)测定核转录因子-κB(NF-κB)通路中NF-κB p65,NF-κB抑制蛋白α(IκBα),丝裂原活化蛋白激酶(MAPK)通路中c-Jun氨基末端激酶(JNK),p38,细胞外调节蛋白激酶(ERK1/2)及其磷酸化蛋白表达。结果:与正常组比较,模型组小鼠肺组织出现明显损伤,其中大量炎性细胞浸润,且肺泡完整性被破坏。BALF中炎性因子TNF-α,IL-6及肺组织NF-κB p65,JNK,p38,ERK1/2磷酸化蛋白表达水平显著升高(P<0.01);与模型组比较,泽漆醇提物高剂量组及地塞米松阳性药组小鼠肺组织病理损伤明显缓解,BALF中TNF-α,IL-6含量及肺组织NF-κB p65,JNK,p38,ERK1/2磷酸化蛋白表达水平显著下调(P<0.01)。结论:泽漆醇提取物对LPS诱导小鼠急性肺损伤具有保护作用,其机制可能与调控MAPK/NF-κB信号通路有关。 Objective: To study the protective effect of Euphorbia helioscopia alcohol extract on lipopolysaccharide(LPS)-induced acute lung injury in mice and explore its possible mechanism. Method: The50 Balb/c male mice were randomly divided into 5 groups, including normal group, model group,dexamethasone group(1.5 mg·kg^-1),E. helioscopia alcohol extracts group(7.5,3.75 g·kg^-1). Except for the normal group,the other groups used intranasal instillation of LPS to establish a model of acute lung injury in mice. The type and number of inflammatory cells in bronchoalveolar lavage fluid(BALF)were detected by automatic blood analyzer and Wright-Giemsa composite staining. The lung tissue damage was observed by hematoxylin-eosin(HE)staining. The contents of the inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in BALF were detected by flow cytometry. The protein expressions of nuclear factor kappa-B p65(NF-κB p65),phospho-NF-κB p65(p-NF-κB p65),inhibitor of NF-κBα(IκBα),phospho-IκBα(p-IκBα)in NF-κB pathway and c-Jun N-terminal kinase(JNK),phospho-JNK(p-JNK),p38 protein(p38),phospho-p38(p-p38),extracellular regulated protein kinases(ERK1/2),phospho-ERK1/2(p-ERK1/2)in mitogen-activated protein kinase(MAPK)pathway were determined by Western blot. Result: Compared with normal control group,the lung tissue of the model group showed obvious damage,in which a large number of inflammatory cells infiltrated,and the integrity of the alveoli was destroyed. Inflammatory factors TNF-α,IL-6 in BALF and p-NF-κB p65,p-JNK,p-p38,p-ERK protein expression levels in lung tissue were significantly increased(P<0.01). Compared with model group,the pathological damage of lung tissue in mice with high dose of E. helioscopia alcohol extract and dexamethasone positive group was significantly alleviated. The levels of TNF-α and IL-6 in BALF and the expression levels of p-NF-κB p65,p-JNK,p-p38 and p-ERK1/2 protein in lung tissue were significantly down-regulated(P<0.01). Conclusion: The E. helioscopia alcohol extr
作者 陈兰英 尹力 周朦静 邵峰 石强 刘荣华 CHEN Lan-ying;YIN Li;ZHOU Meng-jing;SHAO Feng;SHI Qiang;LIU Rong-hua(National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine(TCM),Nanchang 330006,China;School of Pharmacy,Jiangxi University of TCM,Nanchang 330004,China;Qihuang Academy of TCM,Jiangxi University of TCM,Nanchang 330025,China)
出处 《中国实验方剂学杂志》 CAS CSCD 北大核心 2020年第20期46-51,共6页 Chinese Journal of Experimental Traditional Medical Formulae
基金 国家自然科学基金项目(81560637) 江西省重点研发计划项目(20181ACG70014) 江西省中药学一流学科专项科研基金项目(JXSYLXK-ZHYAO124)。
关键词 泽漆醇提物 脂多糖 急性肺损伤 炎症 丝裂原活化蛋白激酶/核转录因子-κB(MAPK/NF-κB)通路 Euphorbia helioscopia alcohol extracts lipopolysaccharide acute lung injury inflammation mitogen-activated protein kinase/nuclear factor kappa-B(MAPK/NF-κB)pathway
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