双氢青蒿素对小鼠肺纤维化的影响及作用机制  

Effect of dihydroartemisinin on mouse pulmonary fibrosis model and its mechanism

作　　者：白君 陈珠妮 叶景焕 熊广[2] 李亚清[2] 谢纬[2] BAI Jun;CHEN Zhuni;YE Jinghuan;XIONG Guang;LI Yaqing;XIE Wei(The Fourth Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518000,Guangdong,China;Shenzhen Hospital of Traditional Chinese Medicine,Shenzhen 518000,Guangdong,China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518000 [2]深圳市中医院,广东深圳518000

出　　处：《中南医学科学杂志》2023年第6期848-852,952,共6页Medical Science Journal of Central South China

基　　金：深圳市科技创新专项基金项目(JSGG20220226090002003);深圳市“医疗卫生三名工程”项目(SZSM201812063)。

摘　　要：目的探讨双氢青蒿素对小鼠肺纤维化的影响及其可能机制。方法将SPF小鼠35只随机分成空白对照组、模型组、甲泼尼龙组、双氢青蒿素低、高剂量组,每组7只;成模后,分别用药物治疗14天后处死小鼠,取肺脏标本进行肺泡炎症、肺纤维化评分和羟脯氨酸测定。培养成纤维细胞,分为对照组、甲泼尼龙低、高剂量组、双氢青蒿素低、中、高剂量组,分别给与药物处理,MTS法检测成纤维细胞增殖率,蛋白质印迹法测定成纤维细胞相关蛋白水平。结果双氢青蒿素组及甲泼尼龙组肺泡炎症、纤维化评分和羟脯氨酸含量均明显低于模型组;双氢青蒿素组和甲泼尼龙组抑制NIH3T3细胞增殖能力,且呈时间、剂量依赖性;各剂量双氢青蒿素组和甲泼尼龙组均可下调MMP-2和Cyclin D1蛋白及上调TIMP1表达,且一定范围内呈剂量依赖性。结论小鼠肺泡炎症和肺纤维化程度能被双氢青蒿素有效减轻,同时成纤维细胞的增殖可被其抑制,在一定范围内上述效应与药物剂量相关。Aim A pulmonary fibrosis model was established to observe the effect of DHA on the degree of alveolar catarrh and pulmonary fibrosis,and to explore the effect of different concentrations of DHA on NIH3T3 fibroblast proliferation and its possible mechanisms.Methods 35 SPF mice,randomly divided into blank contrast group,model group,methylpredillone group,DHA of low,high concentration group,with 7 mice in each group.After the establishment of the model,lung samples were taken after 14 days of drug treatment for alveolar catarrh,lung fibrosis score and hydroxyproline determination.Fibroblasts were cultured and divided into contrast group,low and high doses of methylprednisolone group and dihydroartemisinin group of low,medium and high doses,respectively.These groups were treated with drugs,and then fibroblast proliferation rate were determined by MTS,while fibroblast-associated protein levels were determined by Western blotting.Results score of alveolar catarrh,fibrosis and content of hydroxyproline were significantly lower in dihydroartemisinin and meprednisolone group than in model group.Dihydroartemisinin and prednisolone group showed inhibited proliferation of NIH3T3 cells relating to time and doses.All doses of dihydroartemisinin and methylprednisolone groups showed downregulated MMP-2 and Cyclin D1 protein and upregulated TIMP1 expression,correlated with drug concentrations in a certain range.Conclusion Dihydroartemisinin could effectively reduce the degree of the alveolar catarrh and pulmonary fibrosis induced by bleomycin,and inhibit the proliferation of fibroblasts.The above effects are related to drug doses within a certain range.

关 键 词：双氢青蒿素 肺纤维化 NIH3T3成纤维细胞 

分 类 号：R563.1[医药卫生—呼吸系统]