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右美托咪定通过调节MALAT1/miR-126-5p/HMGB1轴减轻肝缺血/再灌注损伤

马新刚, 刘叶, 薛明喜^*

淄博市妇幼保健院手术麻醉科，淄博 255000

摘要

本文旨在探究右美托咪定(dexmedetomidine, Dex)在肝脏缺血再灌注损伤(hepatic ischemia/reperfusion injury, HIRI)过程中的作用及其机制。将人正常肝细胞(HL-7702细胞)在低氧条件下培养24 h，再在复氧条件下培养12 h，用实时定量PCR (quantitative real-time PCR, qRT-PCR)和Western blot检测长链非编码RNA MALAT1、microRNA-126-5p (miR-126-5p)和高迁移率族蛋白-1 (high mobility group box-1, HMGB1)的表达水平。用生物信息学预测方法和双荧光素酶基因报告实验分析miR-126-5p与MALAT1、HMGB1的靶向关系。用试剂盒分别检测细胞培养液中活性氧(reactive oxygen species, ROS)、丙二醛(malondialdehyde, MDA)和ATP的水平。结果显示，Dex能显著降低HL-7702细胞HIRI后培养液中ROS和MDA的水平，提高ATP的水平。HIRI可上调细胞MALAT1和HMGB1的表达，下调miR-126-5p的表达，而Dex可逆转HIRI的上述作用。Dex可抑制HIRI诱导的细胞凋亡，而过表达MALAT1可逆转Dex的抑制作用，上调miR-126-5p表达水平可恢复Dex的此作用。以上结果提示，Dex可通过调节MALAT1/miR-126-5p/HMGB1轴在HIRI中发挥保护作用。

关键词： 右美托咪定; 肝缺血再灌注损伤; MALAT1; miR-126-5p; 高迁移率族蛋白-1

分类号：R333.4

Dexmedetomidine alleviates hepatic ischemia-reperfusion injury by regulating MALAT1/miR-126-5p/HMGB1 axis

MA Xin-Gang, LIU Ye, XUE Ming-Xi^*

Department of Anesthesiology, Zibo Maternal and Child Health Hospital, Zibo 255000, China

Abstract

The aim of this study was to investigate the effects of dexmedetomidine (Dex) on hepatic ischemia/reperfusion injury (HIRI) and the underlying mechanism. The in vitro HIRI was induced by culturing HL-7702 cells, a human hepatocyte cell line, under 24 h of hypoxia and 12 h of reoxygenation. Quantitative real time PCR (qRT-PCR) and Western blot were performed to detect the expression levels of long non-coding RNA MALAT1, microRNA-126-5p (miR-126-5p) and high mobility group box-1 (HMGB1). Bioinformatics prediction and double luciferase assay were used to verify the targeting relationship between miR-126-5p and MALAT1, HMGB1. Reactive oxygen species (ROS), malondialdehyde (MDA) and ATP levels in culture medium were detected by corresponding kits. The results showed that Dex significantly reduced the levels of ROS and MDA, but increased the level of ATP in HL-7702 cells with HIRI. HIRI up-regulated the expression levels of MALAT1 and HMGB1, and down-regulated the level of miR-126-5p. Dex reversed these effects of HIRI. Furthermore, Dex inhibited HIRI-induced cellular apoptosis, whereas MALAT1 reversed the effect of Dex. This inhibitory effect of Dex could be restored by up-regulation of miR-126-5p. The results suggest that Dex protects hepatocytes from HIRI via regulating MALAT1/miR-126-5p/HMGB1 axis.

Key words: dexmedetomidine; hepatic ischemia/reperfusion injury; MALAT1; miR-126-5p; high mobility group box-1

收稿日期：2020-05-25　　录用日期：2020-11-04

通讯作者：薛明喜　　E-mail: xmxi1964@126.com

DOI: 10.13294/j.aps.2021.0019

引用本文：

马新刚, 刘叶, 薛明喜. 右美托咪定通过调节MALAT1/miR-126-5p/HMGB1轴减轻肝缺血/再灌注损伤[J]. 生理学报 2021; 73 (2): 253-262.

MA Xin-Gang, LIU Ye, XUE Ming-Xi. Dexmedetomidine alleviates hepatic ischemia-reperfusion injury by regulating MALAT1/miR-126-5p/HMGB1 axis. Acta Physiol Sin 2021; 73 (2): 253-262 (in Chinese with English abstract).