Orally administered BZL-s RNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice  

作　　者：Dandan Zhao Yuhao Qin Jiaqi Liu Kegong Tang Shuaiyao Lu Zirui Liu Yexuan Lin Cong Zhang Fengming Huang Jiahui Chang Chang Li Mingyao Tian Yiming Ma Xiaoyun Li Congzhao Zhou Xiao Li Xiaozhong Peng Ningyi Jin Chengyu Jiang 

机构地区：[1]State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Biochemistry,Peking Union Medical College,Beijing 100005,China [2]Institute of Medical Biology,Chinese Academy of Medical Sciences,Kunming 650031,China [3]Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences,University of Science and Technology of China,Hefei 230027,China [4]Changchun Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Changchun 130122,China

出　　处：《Science China(Life Sciences)》2023年第7期1589-1599,共11页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(81788101);the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-022);the CAMS Endowment Fund(2021-CAMS-JZ001);the Overseas Expertise Introduction Center for Discipline Innovation(“111Center”)(BP0820029);the State Key Laboratory Special Fund of State Key Laboratory of Medical Molecular Biology(2060204)。

摘　　要：The global COVID-19 pandemic emerged at the end of December 2019.Acute respiratory distress syndrome(ARDS)and acute lung injury(ALI)are common lethal outcomes of bacterial lipopolysaccharide(LPS),avian influenza virus,and SARS-Co V-2.Toll-like receptor 4(TLR4)is a key target in the pathological pathway of ARDS and ALI.Previous studies have reported that herbal small RNAs(s RNAs)are a functional medical component.BZL-s RNA-20(Accession number:B59471456;Family ID:F2201.Q001979.B11)is a potent inhibitor of Toll-like receptor 4(TLR4)and pro-inflammatory cytokines.Furthermore,BZLs RNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid(LTA)and polyinosinic-polycytidylic acid(poly(I:C)).We found that BZL-s RNA-20 rescued the viability of cells infected with avian influenza H5N1,SARS-Co V-2,and several of its variants of concern(VOCs).Acute lung injury induced by LPS and SARS-Co V-2 in mice was significantly ameliorated by the oral medical decoctosome mimic(bencaosome;sphinganine(d22:0)+BZL-s RNA-20).Our findings suggest that BZLs RNA-20 could be a pan-anti-ARDS/ALI drug.

关 键 词：oligonucleotide drug herbal medicine ARDS/ALI SARS-CoV-2 

分 类 号：R965[医药卫生—药理学]