右美托咪定通过 Nrf2/HO-1 通路减轻小鼠全身放射诱导的急性肝损伤。

Dexmedetomidine Attenuates Total Body Radiation-Induced Acute Liver Injury in Mice Through the Nrf2/HO-1 Pathway.

出版信息

Clin Lab. 2022 Aug 1;68(8). doi: 10.7754/Clin.Lab.2022.220310.

DOI:10.7754/Clin.Lab.2022.220310

Abstract

BACKGROUND

The purpose of this study was to investigate the protective effects of dexmedetomidine (DEX) on total body radiation-induced acute liver injury in mice and to explore the possible mechanisms.

METHODS

A total of 40 mice were randomly divided into the Control group (Group C), Dexmedetomidine group (Group Dex), Radiation group (Group R), and Group R+Dex. Mice in Group Dex and Group R+Dex were intraperitoneally injected with 10 µg/mL Dex at 50 mg/kg. Both Group C and Group R received normal saline instead of Dex. Mice were treated via continuous administration for 10 days and injection once a day (pre-administration for 3 days and 7 days after radiation). One hour after administration on the third day, the mice in Group R and R+Dex received total body radiation with a total dose of 6 Gy at a rate of 2 Gy/min. Group C received sham radiation. Levels of aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and liver levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured. HE staining was employed to evaluate the pathological changes in liver tissues, and the expressions of Nrf2 and HO-1 proteins in the liver were measured by western blot.

RESULTS

Compared with group C, serum levels of AST and ALT, liver TNF-α, IL-1β, MDA, and ROS levels increased, and SOD decreased in Group R. Group R mice had higher liver injury scores, and the protein expressions of Nrf2 and HO-1 proteins were lower (p ＜ 0.05). Compared with Group R, the levels of AST, ALT, TNF-α, IL-1β, MDA, and ROS decreased, SOD increased, liver injury scores were lower, and the expressions of Nrf2 and HO-1 proteins were higher in the Group R+Dex group (all p ＜ 0.05).

CONCLUSIONS

Dex exhibits a protective effect on reducing acute radiation-induced liver injury and oxidative stress, and the mechanism may be associated with the activation of Nrf2/HO-1 pathways.

摘要

背景

本研究旨在探讨右美托咪定（DEX）对小鼠全身辐射性急性肝损伤的保护作用，并探讨可能的机制。

方法

将 40 只小鼠随机分为对照组（C 组）、DEX 组（D 组）、辐射组（R 组）和 R+DEX 组。DEX 组和 R+DEX 组小鼠腹腔注射 10μg/mL、50mg/kg 的 DEX。C 组和 R 组给予生理盐水代替 DEX。连续给药 10 天，每天 1 次（辐射前 3 天和后 7 天）。第 3 天给药 1 小时后，R 组和 R+DEX 组小鼠接受全身 6Gy 照射，剂量率为 2Gy/min。C 组接受假照射。检测血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、肝组织肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）、活性氧（ROS）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平。采用 HE 染色评估肝组织病理变化，Western blot 法检测肝组织 Nrf2 和 HO-1 蛋白表达。

结果

与 C 组比较，R 组血清 AST、ALT 水平，肝 TNF-α、IL-1β、MDA、ROS 水平升高，SOD 水平降低；肝损伤评分升高，Nrf2 和 HO-1 蛋白表达降低（P＜0.05）。与 R 组比较，R+DEX 组血清 AST、ALT 水平，肝 TNF-α、IL-1β、MDA、ROS 水平降低，SOD 水平升高，肝损伤评分降低，Nrf2 和 HO-1 蛋白表达升高（均 P＜0.05）。