Background: Dexmedetomidine (Dex), frequently used as an effective sedative, was reported to play a critical role in the protection of multiple organs. However, its underlying mechanism of a putative protective effect on ischemia/reperfusion (I/R)-induced liver injury is still unclear. Methods: A hepatocyte injury model was established by treating WRL-68 cells with oxygen and glucose deprivation/reoxygenation (OGD/R). Enzyme Linked Immunosorbent Assay (ELISA) kits were used to determine the level of inflammatory factors (IL-6, IL-1β, and TNF-α), and oxidative stress indicators (ROS, MDA, GSH-Px, and SOD). MTT assay and flow cytometry analysis were used to determine the influence of Dex on cell viability and cell apoptosis. Expression of nuclear factor erythroid-derived 2- like 2 (Nrf2), HO-1, and apoptosis-related proteins (Bax, Bcl-2, caspase3, and caspase9) were detected by qRT-PCR and western blotting. Results: Dex promoted cell viability and suppressed cell apoptosis in OGD/R-treated WRL-68 cells. Dex reduced TNF-α, IL-6, IL-1β, ROS, and MDA production, whereas it increased that of SOD and GSH-Px in OGD/R-treated WRL-68 cells. Moreover, Nrf2, HO-1, and Bcl-2 expression was upregulated, whereas, in contrast, transcripts for Bax, caspase3, and caspase9 were downregulated following Dex treatment under OGD/R. Knockdown of Nrf2 reversed the Dex effects on cell proliferation, apoptosis, and expression of TNF-α, IL-6, IL-1β, ROS, MDA, SOD, and GSH-Px. Conclusion: Dex protects WRL-68 cells against OGD/R-induced injury by inhibiting inflammation, oxidative stress, and cell apoptosis via the activation of Nrf2/HO-1 signaling pathway, suggesting that Dex may be a potential protector against hepatic injury.

中文翻译：

---

右美托咪定通过抑制氧化应激和激活Nrf2 / HO-1信号通路来减轻肝损伤。

背景：经常被用作有效的镇静剂的右美托咪定（Dex）在保护多种器官中起着至关重要的作用。然而，其对缺血/再灌注（I / R）诱导的肝损伤的潜在保护作用的潜在机制仍不清楚。方法：以氧和葡萄糖剥夺/复氧（OGD / R）处理WRL-68细胞，建立肝细胞损伤模型。酶联免疫吸附测定（ELISA）试剂盒用于确定炎症因子（IL-6，IL-1β和TNF-α）和氧化应激指标（ROS，MDA，GSH-Px和SOD）的水平。使用MTT测定和流式细胞术分析来确定Dex对细胞生存力和细胞凋亡的影响。核因子类红细胞衍生的2-like 2（Nrf2），HO-1和凋亡相关蛋白（Bax，Bcl-2，caspase3，用qRT-PCR和western blotting检测caspase9和caspase9）。结果：Dex促进了OGD / R处理的WRL-68细胞的细胞活力并抑制了细胞凋亡。Dex降低了OGD / R处理的WRL-68细胞中TNF-α，IL-6，IL-1β，ROS和MDA的产生，而增加了SOD和GSH-Px的产生。此外，在OGD / R下进行Dex处理后，Nrf2，HO-1和Bcl-2的表达上调，而Bax，caspase3和caspase9的转录本下调。击倒Nrf2可逆转Dex对细胞增殖，凋亡和TNF-α，IL-6，IL-1β，ROS，MDA，SOD和GSH-Px表达的影响。结论：Dex通过激活Nrf2 / HO-1信号通路抑制炎症，氧化应激和细胞凋亡，从而保护WRL-68细胞免受OGD / R诱导的损伤，