Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Int Immunopharmacol. 2020 Dec;89(Pt B):107095. doi: 10.1016/j.intimp.2020.107095. Epub 2020 Oct 20.
Hypoxia and the resultant decreases in cerebral blood flow in the perinatal period can lead to neonatal hypoxic-ischemic (HI) brain injury, which can, in turn, cause severe disability or even death. However, the efficacy of current treatment strategies remains limited. Several studies have demonstrated that lipoxin A4 (LXA4), as one of the earliest types of endogenous lipid mediators, can inhibit the accumulation of neutrophils, arrest inflammation, and promote the resolution of inflammation. However, research on LXA4 in the nervous system has rarely been carried out. In the present study, we sought to investigate the protective effect of LXA4 on HI brain damage in neonatal rats, as well as the underlying mechanisms. Through experiments conducted using an HI animal model, we found that the LXA4 intervention promoted the recovery of neuronal function and tissue structure following brain injury while maintaining the integrity of the blood-brain barrier in addition to reducing cerebral edema, infarct volume, and inflammatory responses. Our results suggest that LXA4 interfered with neuronal oxygen-glucose deprivation insults, reduced the expression of inflammatory factors, inhibited apoptosis, and promoted neuronal survival in vitro. Finally, the LXA4 intervention attenuated HI-induced activation of inhibitor kappa B (IκB) and degradation of nuclear factor-κB (NF-κB). In conclusion, our data suggest that LXA4 exerts a neuroprotective effect against neonatal HI brain damage through the IκB/NF-κB pathway. Our findings will help inform future studies regarding the effects of LXA4 on neuroinflammation, blood-brain barrier integrity, and neuronal apoptosis.
缺氧和由此导致的围产期脑血流减少可导致新生儿缺氧缺血性（HI）脑损伤，进而导致严重残疾甚至死亡。然而，目前治疗策略的疗效仍然有限。几项研究表明，脂氧素 A4（LXA4）作为最早的内源性脂质介质之一，可以抑制中性粒细胞的积累，阻止炎症，并促进炎症的消退。然而，关于 LXA4 在神经系统中的研究很少。在本研究中，我们试图研究 LXA4 对新生大鼠 HI 脑损伤的保护作用及其潜在机制。通过使用 HI 动物模型进行的实验，我们发现 LXA4 干预促进了脑损伤后神经元功能和组织结构的恢复，同时保持了血脑屏障的完整性，减少了脑水肿、梗死体积和炎症反应。我们的结果表明，LXA4 干扰神经元的氧葡萄糖剥夺损伤，降低炎症因子的表达，抑制细胞凋亡，并促进体外神经元的存活。最后，LXA4 干预减轻了 HI 诱导的抑制因子 kappa B（IκB）的激活和核因子-κB（NF-κB）的降解。总之，我们的数据表明，LXA4 通过 IκB/NF-κB 途径对新生儿 HI 脑损伤发挥神经保护作用。我们的发现将有助于为未来关于 LXA4 对神经炎症、血脑屏障完整性和神经元凋亡影响的研究提供信息。
