RESUMO
OBJECTIVE: This study was probed to uncover the mechanism of miR-142-5p in septic liver injury. MATERIALS AND METHODS: In this study, in-vitro and in-vivo models of sepsis were used. For in-vitro sepsis model, hepatocyte cell line (L02 cells) was treated with LPS (lipopolysaccharide). Whereas for in-vivo sepsis model, cecal ligation and puncture were performed in mice. Mice were assigned into three groups: control, CLP (Cecal Ligation Puncture), CLP + miR-142-5p inhibitor group. Liver injury was assessed via H&E staining. IL-6, TNF-α, and IL-1ß expressions were assayed through ELISA kits. C-caspase-9, C-caspase-3, ERK, p65, and IκBα expressions were determined via western blot and RT-qPCR. Apoptosis in LPS-induced L02 cells was detected by TUNEL staining. RESULTS: Our results show that miR-142-5p exhibited perspicuous upregulation in CLP mice tissues and LPS-induced L02 cells. On the other hand, inhibition of miR-142-5p could promote LPS-induced L02 cell activity and reduce apoptosis and inflammation. In terms of molecular mechanism, downregulation of miR-142-5p could abate sepsis-mediated acute hepatic injury by targeting SOCS1, through ERK and NF-κB pathway. CONCLUSIONS: Overall our results demonstrate that miR-142-5p inhibitors can mitigate septic liver injury by downregulating the inflammation and apoptosis via targeting SOCS1. Thus, miR-142-5p can serve a potential therapeutic target for sepsis mediated acute hepatic injury.
Assuntos
Hepatócitos/patologia , Falência Hepática/fisiopatologia , MicroRNAs/genética , Sepse/complicações , Animais , Apoptose/fisiologia , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Inflamação/etiologia , Inflamação/patologia , Lipopolissacarídeos , Falência Hepática/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para CimaRESUMO
The traditional Chinese medicine Nao Li Shen (containing ginseng, gastrodia tuber, chuanxiong rhizome and red sage root) is used in craniocerebral injury, cervical spondylosis and cerebrovascular diseases. The preparation, as an orally administered liquid, was tested in Mongolian gerbils and shown to increase tolerance to ischaemia and anoxia. Clinical use of the preparation resulted in improvement in 96% of 202 patients, as judged by right cerebral blood flow, TCD and CT examination. We conclude that Nao Li Shen has a positive curative effect upon craniocerebral injury and sequelae of cerebrovascular diseases.