中国药理学与毒理学杂志2024，Vol.38Issue(11)：826-833,8.DOI:10.3867/j.issn.1000-3002.2024.11.003
脂质纳米粒递送IL-35 mRNA对脂多糖诱导小鼠急性肺损伤的保护作用
Protective effect of IL-35 mRNA deliveried by lipid nanoparticles against lipopolysaccharide induced acute lung injury in mice
摘要
Abstract
OBJECTIVE To investigate the protective effect of interleukin-35(IL-35)mRNA-lipid nanoparticles(LNP)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.METHODS Fifity-six mice were randomly divided into 7 groups with 8 mice in each,including the normal control group,IL-35 mRNA-LNP(250 μg·kg-1)group,LPS group,LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group and LPS+Dexamethasone(DXM)group.Except for the normal control group and IL-35 mRNA-LNP(250 μg·kg-1)group and ALI model was established by tracheal infusion of LPS in each of the other groups.IL-35 mRNA-LNP(250 μg·kg-1)group and LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group were injected with a corresponding dose of LNP encapsulated mRNA complex via the tail vein while the LPS+DXM group was injected with DXM via the tail vein.Lung coefficient and the wet to dry weight ratio(W/D)of lung tissue were recorded.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α),Interleukin-6(IL-6)and IL-1βof lung homogenates were detected by real-time fluorescence quantitative PCR(RT-qPCR).LDH activity of lung homogenates and the protein levels of IL-35,TNF-α,IL-6 and IL-1β in lung homogenate were detected by corresponding kits.Hematoxylin-eosin(HE)staining was used to observe and analyze the pathological injury to lung tissue.The expres-sion of Lymphocyte antigen 6G(Ly6G)was detected by Immunofluorescence to reflect the infiltration of neutrophils.RESULTS Compared with the normal control group,LPS group and LPS+DXM group,IL-35 protein expression levels in lung homogenates of the other groups were more significant(P<0.01).Compared with the normal control group,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were significantly increased in the LPS group(P<0.01),accompanied by alveolar hemorrhage,alveolar wall thickening and neutro-phils infiltration.After IL-35 mRNA-LNP administration,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were signifi-cantly decreased(P<0.01),and alveolar hemorrhage,alveolar wall thickening and neutrophil infiltration were obviously improved.CONCLUSION IL-35 mRNA-LNP can express IL-35 protein in lung tissue of mice,and effectively improve LPS-induced ALI in mice by inhibiting the expression of proinflammatory factors.关键词
白细胞介素35/mRNA/脂质纳米粒/脂多糖/急性肺损伤/炎症Key words
IL-35/mRNA/lipid nanoparticles/lipopolysaccharide/acute lung injury/inflammation分类
医药卫生引用本文复制引用
麦洁锐,孙会胜,廖宇钦,李燕燕,王淑美,杨静,王升启..脂质纳米粒递送IL-35 mRNA对脂多糖诱导小鼠急性肺损伤的保护作用[J].中国药理学与毒理学杂志,2024,38(11):826-833,8.基金项目
国家重点研发计划(2021YFC2302405) National Key Research and Development Program of China(2021YFC2302405) （2021YFC2302405）
