Department of Physiology and Pharmacology, Stockholm, Sweden; Department of Medicine, Division of Nephrology, Durham, NC, USA.
Department of Physiology and Pharmacology, Stockholm, Sweden.
Br J Anaesth. 2019 Mar;122(3):350-360. doi: 10.1016/j.bja.2018.10.062. Epub 2018 Dec 28.
Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice.
Adult male C57BL/6 (n=111) and Ccr2Cx3cr1 (n=54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery. Systemic inflammatory changes, bone healing, neuroinflammation, and cognition were assessed at different time points. MaR1 protective effects were also evaluated using bone marrow derived macrophage cultures.
MaR1 exerted potent systemic anti-inflammatory effects without impairing fracture healing. Prophylaxis with MaR1 prevented surgery-induced glial activation and opening of the blood-brain barrier. In Ccr2Cx3cr1 mice, fewer infiltrating macrophages were detected in the hippocampus after surgery with MaR1 prophylaxis, which resulted in improved memory function. MaR1 treatment also reduced expression of pro-inflammatory cell surface markers and cytokines by in vitro cultured macrophages. MaR1 was detectable in the cerebrospinal fluid of older adults before and after surgery.
MaR1 exerts distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-κB signalling, and cytokine release after surgery. Future studies on the use of pro-resolving lipid mediators may inform novel approaches to treat neuroinflammation and postoperative neurocognitive disorders.
炎症反应的解决是手术后一个主动和动态的过程。maresin 1（MaR1）是越来越多由巨噬细胞生物合成的具有特殊作用的促解决脂质之一，它调节急性炎症。我们研究了 MaR1 对手术后神经炎症、巨噬细胞活性和小鼠认知功能的影响。
成年雄性 C57BL/6（n=111）和 Ccr2Cx3cr1（n=54）小鼠在接受麻醉和矫形手术后用 MaR1 进行治疗。在不同时间点评估全身炎症变化、骨愈合、神经炎症和认知。还使用骨髓来源的巨噬细胞培养物评估 MaR1 的保护作用。
MaR1 发挥了强大的全身抗炎作用，而不会损害骨折愈合。MaR1 预防可预防手术引起的神经胶质激活和血脑屏障开放。在 Ccr2Cx3cr1 小鼠中，用 MaR1 预防可减少手术后海马中的浸润巨噬细胞，从而改善记忆功能。MaR1 治疗还降低了体外培养的巨噬细胞中促炎细胞表面标志物和细胞因子的表达。MaR1 可在老年人手术前后的脑脊液中检测到。
MaR1 通过调节手术后巨噬细胞浸润、NF-κB 信号和细胞因子释放，发挥独特的抗炎和促解决作用。关于使用促解决脂质介质的未来研究可能会为治疗神经炎症和术后神经认知障碍提供新的方法。
