摘要
目的制备一种新型花形乳糖药用载体装载环黄芪醇的纳米颗粒,探讨其在体内/外的抗病毒作用。方法筛选环黄芪醇-花形乳糖纳米颗粒的最优制备工艺,考察其溶解度和释药性能。建立急性病毒性心肌炎小鼠模型和新冠病毒性肺炎小鼠体内/外模型,使用环黄芪醇-花形乳糖对模型进行干预,观察其病理学改变,检测炎症因子及细胞凋亡的改变情况。结果环黄芪醇-花形乳糖体外溶解度是环黄芪醇单体的4.33倍;1、48 h体外累积释药率分别是环黄芪醇单体的3.70、2.24倍。与心肌炎模型组小鼠相比,环黄芪醇-花形乳糖可抑制白细胞介素-6(interleukin-6,IL-6)、白细胞介素-17(interleukin-17,IL-17)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、中性粒细胞胞外陷阱(neutrophil extracellular traps,NETs)表达(P<0.05),降低心肌组织匀浆中柯萨奇B3病毒(coxsackievirus B3,CVB3)毒力(P<0.05),减轻心肌组织损伤与炎症细胞浸润,下调病理评分(P<0.05)。与新冠病毒肺炎模型组比较,环黄芪醇-花形乳糖可抑制白细胞介素-1(interleukin-6,IL-1)、TNF-α、NETs的表达(P<0.05),减轻肺组织间质水肿与炎症细胞浸润,下调病理评分(P<0.05)。体外细胞模型上,与病毒感染细胞相比,环黄芪醇-花形乳糖可明显下调细胞凋亡的比例(P<0.05)。结论本研究制备的环黄芪醇-花形乳糖纳米颗粒性质稳定,具有较好溶解性和释药性能;在心肌炎小鼠模型和新冠病毒肺炎小鼠模型上均能抑制炎症反应,有效减轻靶器官损伤。
Objective A new nanoparticle of flower-shaped lactose(FL)loaded with Cycloastragenol(CAG)was prepared,preliminary study of antiviral effects in vitro/in vivo.Methods The optimal process for screening CAG-FL nanoparticles to investigate their solubility and drug release properties.A mouse model of viral myocarditis in vitro and a mouse model of COVID-19 pneumonia were established.CAG-FL was used to intervene the model,and the intervention effect was evaluated by pathological evaluation and detection of inflammatory factors and cell apoptosis.Results The in vitro solubility of CAG-FL is 4.33 times that of CAG monomer;The cumulative in vitro release rates at 1 and 48 hours were 3.7 and 2.24 times higher than the CAG monomer,respectively.In the mouse model of myocarditis,compared with the virus group,CAG-FL could significantly inhibit inflammatory factor release(P<0.05),reduce viral virulence(P<0.05),and improve myocardial damage(P<0.05);In the in vitro/in vivo model of novel coronavirus pneumonia,CAG-FL improved interstitial edema and inflammatory cell infiltration in lung tissue(P<0.05)and inhibited apoptosis induced by novel pseudovirus(P<0.05),Inhibit the apoptosis induced by the novel coronavirus pseudovirus(P<0.05).Conclusions CAG-FL has stable physicochemical properties,good solubility and drug release properties;it can inhibit inflammation and effectively improve target organ damage in both myocarditis and novel coronavirus pneumonia mouse models.
作者
虞勇
李明辉
虞雅妮
王宇成
刘潇潇
石卉
陈治伟
喻思佳
陈瑞珍
YU Yong;LI Minghui;YU Yani;WANG Yucheng;LIU Xiaoxiao;SHI Hui;CHEN Zhiwei;YU Sijia;CHEN Ruizhen(Zhongshan Hospital,Fudan University,Shanghai Institute of Cardiovascular Diseases,Shanghai 200032,China;Shanghai First People's Hospital,Shanhai Jiao Tong University,Shanghai 200080,China)
出处
《中国分子心脏病学杂志》
2025年第3期6868-6874,共7页
Molecular Cardiology of China
基金
上海市科技创新计划(22S21903300)
国家自然科学基金(82370361)
中山医院临床研究专项基金(2020ZSLC10)
中山医院科研发展基金(2022ZSFZ11)。
关键词
环黄芪醇
花形乳糖
病毒性心肌炎
新冠病毒肺炎
抗病毒作用
Cycloastragenol
Flower-shaped lactose
Viral myocarditis
COVID-19 pneumonia
Antiviral activity
