摘要
2019年12月底,新型冠状病毒病(coronavirus disease 2019,COVID-19)开始流行.急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)和急性肺损伤(acute lung injury,ALI)是由细菌脂多糖(lipopolysaccharide,LPS)、禽流感病毒和新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)等引发的高致死疾病.Toll样受体4(Toll-like receptor 4,TLR4)是ARDS和ALI病理通路中的关键靶点.草药小RNA(small RNA,sRNA)已被报道是草药药效的重要成分之一.本研究发现,半枝莲来源的小核酸BZL-sRNA-20(检索号:B59471456;ID:F2201.Q001979.B11)是TLR4及促炎细胞因子的有效抑制剂,可下调细菌脂磷壁酸(lipoteichoic acid,LTA)和聚肌苷酸-聚胞苷酸(Poly(I∶C))引发上升的促炎细胞因子水平,并能挽救禽流感病毒H5N1,SARS-CoV-2及其多种变异株感染所致的细胞死亡.此外,口服本草体(bencaosome)∶(鞘氨醇(d22∶0)+BZL-sRNA-20)可缓解LPS与SARS-CoV-2诱导的小鼠急性肺损伤.本研究结果表明,半枝莲来源的BZL-sRNA-20可能是一种广谱治疗ARDS/ALI的寡核苷酸药物.
Abstract
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-CoV-2 infection.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(sRNAs)are a functional medical component.BZL-sRNA-20(Accession number:B59471456;Family ID:F2201.Q001979.B11)is a potent inhibitor of Toll-like receptor 4(TLR4)and pro-inflammatory cytokines.Furthermore,BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid(LTA)and polyinosinic-polycytidylic acid(poly(I∶C)).We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1,SARS-CoV-2,and several of its variants of concern(VOCs).Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic(bencaosome;sphinganine(d22∶0)+BZL-sRNA-20).Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS/ALI drug.
基金项目
国家自然科学基金(81788101)
中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-022)
中国医学科学院捐赠项目(2021-CAMS-JZ001)
高等学校学科创新引智计划2.0(111计划2.0)(BP0820029)
医学分子生物学国家重点实验室专项基金(2060204)
维普
万方数据