Gu Xiao-Xia, Xu Xiao-Xia, Liao Hui-Hua, Wu Ruo-Na, Huang Wei-Ming, Cheng Li-Xia, Lu Yi-Wen, Mo Jian
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, No.57, South People's Avenue, Xiashan District, 524001, Zhanjiang, Guangdong Province, P.R. China.
Operating room, Affiliated Hospital of Guangdong Medical University, 524001, Zhanjiang, Guangdong Province, P.R. China.
J Inflamm (Lond). 2021 May 26;18(1):20. doi: 10.1186/s12950-021-00287-3.
Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism.
In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting.
DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon.
DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment.
肝损伤严重威胁人类健康。同时，盐酸右美托咪定（DEX）可预防肝损伤。然而，DEX介导肝损伤进展的机制尚不清楚。因此，本研究旨在探讨DEX在氧糖剥夺（OGD）处理的肝细胞中的作用及其潜在机制。
为了研究DEX在肝损伤中的作用，用OGD处理WRL-68细胞。通过MTT法检测细胞活力。通过流式细胞术检测细胞凋亡。通过ELISA法检测炎性细胞因子水平。通过双荧光素酶报告基因检测miR-194与TUG1或SIRT1之间的相互作用。通过qPCR或蛋白质印迹法检测基因和蛋白质水平。
DEX显著逆转了OGD诱导的WRL-68细胞炎症和凋亡。同时，DEX处理逆转了OGD对WRL-68细胞中TUG1、SIRT1和miR-194表达的影响。然而，TUG1敲低或miR-194过表达逆转了DEX在OGD处理的WRL-68细胞中的作用。此外，TUG1可通过吸附miR-194促进SIRT1的表达。此外，TUG1敲低促进了OGD诱导的细胞生长抑制和炎症反应，而miR-194抑制剂或SIRT1过表达部分逆转了这一现象。
DEX可通过TUG1/miR-194/SIRT1轴介导抑制OGD诱导的肝细胞凋亡和炎症。因此，本研究可能为DEX在肝损伤治疗中的应用提供科学依据。
