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右美托咪定通过抑制炎症、氧化应激和 NF-κB 减轻高脂血症大鼠心肌缺血再灌注损伤。

Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF-κB.

机构信息

Department of Anesthesiology, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Operating Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Chem Biol Drug Des. 2023 Nov;102(5):1176-1185. doi: 10.1111/cbdd.14324. Epub 2023 Aug 21.

DOI:10.1111/cbdd.14324
PMID:37604597
Abstract

The present study was conducted to determine the protective effect of Dexmedetomidine (DEX) in myocardial ischemia-reperfusion injury in hyperlipidemic rats. Towards this, the effect of DEX was first evaluated on the infarct size and the histopathology of cardiac tissues using TTC and H and E staining, and it was found that DEX significantly improved the infarct size and architecture of the myocardial tissues following the I/R injury. DEX also showed significant improvement in various examined hemodynamic parameters (e.g., LVSP, and ± dp/dt ) in a dose-dependent manner. The lipid profile (LDL, VLDL, TC, TG, and HDL level) of the rats were also found significantly improved in DEX-treated rats. The level of various pro-inflammatory cytokines (IL-1β, IL-6, IL-10, IL-17, and TNF-α), cardiac injury (CK, CK-MB, Troponin I AST, ALT, and LDH), and oxidative stress (MDA, SOD, and GSH) biomarkers were also found to be restored near to the normal in DEX-treated group. It has been found that DEX also significantly reduces apoptosis of rat cardiomyocytes. In western blot analysis, DEX showed a significant reduction in the activation of NF-κB. In conclusion, our study demonstrated the protective effect of Dexmedetomidine in myocardial ischemia-reperfusion injury in hyperlipidemic rats possibly via amelioration of oxidative stress, and inflammation apoptosis.

摘要

本研究旨在探讨右美托咪定(DEX)对高脂血症大鼠心肌缺血再灌注损伤的保护作用。为此,首先通过 TTC 和 H&E 染色评估了 DEX 对梗死面积和心脏组织病理学的影响,结果发现 DEX 显著改善了 I/R 损伤后心肌组织的梗死面积和结构。DEX 还以剂量依赖的方式显著改善了各种检查的血流动力学参数(例如 LVSP 和±dp/dt)。DEX 治疗的大鼠血脂谱(LDL、VLDL、TC、TG 和 HDL 水平)也明显改善。各种促炎细胞因子(IL-1β、IL-6、IL-10、IL-17 和 TNF-α)、心脏损伤标志物(CK、CK-MB、肌钙蛋白 I AST、ALT 和 LDH)和氧化应激标志物(MDA、SOD 和 GSH)的水平在 DEX 治疗组也恢复到接近正常水平。还发现 DEX 还显著减少了大鼠心肌细胞的凋亡。在 Western blot 分析中,DEX 显示 NF-κB 的激活显著减少。综上所述,本研究表明 DEX 对高脂血症大鼠心肌缺血再灌注损伤具有保护作用,可能通过改善氧化应激和炎症凋亡。

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