Department of Pediatric, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
Life Sci. 2021 Jul 15;277:119467. doi: 10.1016/j.lfs.2021.119467. Epub 2021 Mar 31.
Maresin 1 (MaR1) is a pro-resolving lipid mediator that has been reported to have strong regulatory effects on oxidative stress and inflammation. This study aimed to determine the effect of MaR1 on lipopolysaccharide (LPS)-induced sepsis-related cardiac injury and explore its possible mechanisms.
Mice were administered MaR1 or PBS and then treated with LPS or saline for 6 h. Then, cardiac function, cardiac injury markers, cardiac macrophage differentiation, oxidative stress and myocardial cell apoptosis in each group were measured.
MaR1 treatment significantly decreased the serum levels of lactate dehydrogenase (LDH) and kinase isoenzyme (CK-MB) and improved cardiac function in LPS-induced mice. Treatment with MaR1 also inhibited LPS-induced M1 macrophage differentiation and reduced M1 macrophage-related cytokine secretion while promoting M2 macrophage differentiation and increasing M2 macrophage-related inflammatory mediator expression. In addition, MaR1 decreased serum malondialdehyde (MDA) levels and increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), as well as cardiac expression of nuclear factor erythroid-2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), in LPS-induced mice. Furthermore, fewer TUNEL-positive cells were observed in the LPS + MaR1 group than in the LPS group.
Our experimental results show that MaR1 alleviates cardiac injury and protects against cardiac dysfunction and may be beneficial in reducing sepsis-induced cardiac injury.
maresin 1（MaR1）是一种具有强抗炎和抗氧化作用的新型促分解介质。本研究旨在探讨 MaR1 对脂多糖（LPS）诱导的脓毒症相关心肌损伤的作用及其可能的机制。
给予小鼠 MaR1 或 PBS 预处理，然后用 LPS 或生理盐水处理 6 h。然后，测量各组小鼠的心功能、心肌损伤标志物、心肌巨噬细胞分化、氧化应激和心肌细胞凋亡情况。
MaR1 处理可显著降低 LPS 诱导的小鼠血清乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）水平，改善心功能。MaR1 处理还抑制 LPS 诱导的 M1 型巨噬细胞分化，减少 M1 型巨噬细胞相关细胞因子的分泌，同时促进 M2 型巨噬细胞分化，增加 M2 型巨噬细胞相关炎症介质的表达。此外，MaR1 降低了 LPS 诱导的小鼠血清丙二醛（MDA）水平，增加了血清超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平，上调了核因子红细胞 2 相关因子 2（Nrf-2）和血红素加氧酶 1（HO-1）在心肌中的表达。此外，与 LPS 组相比，LPS+MaR1 组的 TUNEL 阳性细胞较少。
我们的实验结果表明，MaR1 可减轻心肌损伤，改善心功能障碍，可能有益于减轻脓毒症引起的心肌损伤。
