摘要
目的通过博来霉素(BLM)诱导的小鼠肺纤维化模型和TGF-β1诱导的人胚肺成纤维细胞(HFL1)模型探究雨生红球藻(HP)对肺纤维化的影响。方法将30只C57BL/6雄性小鼠随机分为5组:对照组(Control)、模型组(BLM)、HP低剂量组(BLM+HP 3 mg/kg)、HP高剂量组(BLM+HP 21 mg/kg)、阳性药物吡非尼酮(PFD)组(BLM+PFD 300 mg/kg),n=6。21 d后检测小鼠呼吸功能、肺组织病理学变化以及纤维化标志物的表达。在5 ng/mL TGF-β1诱导的HFL1模型,分别给予低、中、高剂量的HP(120、180、240μg/mL),以PFD(1.85μg/mL)作为阳性对照药物,培养48 h后,检测纤维化标志物的表达水平。正常组、模型组、HP高剂量组进行mRNA测序和分析。结果HP在呼吸功能、肺组织形态结构、炎性浸润、胶原纤维沉积和纤维化蛋白质的表达方面均能减轻BLM引起的肺功能损伤和组织形态结构的纤维化,且高剂量HP表现出与PFD相似的效果。体外实验也显示,与模型组相比,高剂量HP可降低α-SMA(P<0.01)和FN(P<0.05)的蛋白质表达,以及α-SMA(P<0.05)和FN(P<0.01)mRNA表达,进一步转录组分析显示多个可能参与HP调控肺纤维化的关键基因和通路。结论HP粉末在体内外均表现出改善肺纤维化的作用,可能通过多种活性物质发挥协同作用,这为肺纤维化疾病的预防和治疗提供了研究基础。
Objective To investigate the effect of Haematococcus pluvialis(HP)on bleomycin(BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts(HFL1).Methods Thirty male C57BL/6 mice were randomly divided into control group,BLM-induced pulmonary fibrosis model group,low-and high-dose HP treatment groups(3 and 21 mg/kg,respectively),and 300 mg/kg pirfenidone(positive control)group.The effects of drug treatment for 21 days were assessed by examining respiratory function,lung histopathology,and expression of fibrosis markers in the lung tissues of the mouse models.In TGF-β1-induced HFL1 cell cultures,the effects of treatment with 120,180 and 240μg/mL HP or 1.85μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated.Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240μg/mL HP.Results HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice,evidenced by improved respiratory function,lung tissue morphology and structure,inflammatory infiltration,and collagen deposition and reduced expressions of fibrotic proteins.HP at the high dose produced similar effect to PFD.In TGF-β1-induced HFL1 cells,treatment with 240μg/mL HP significantly reduced the mRNA and protein expression levels ofα-SMA and FN.Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis.Conclusion HP alleviates pulmonary fibrosis in both the mouse model and cell model,possibly as the result of the synergistic effects of its multiple active components.
作者
张潇
满景洲
张勇
郑云剑
王和平
袁怡君
谢曦
ZHANG Xiao;MAN Jingzhou;ZHANG Yong;ZHENG YunJian;WANG Heping;YUAN Yijun;XIE Xi(Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou 570228,China;Alphy Biotechnology(Jiaxing)Co.,LTD,Jiaxing 314422,China)
出处
《南方医科大学学报》
北大核心
2025年第8期1672-1681,共10页
Journal of Southern Medical University
基金
海南省自然科学基金(822MS053)。
