目的:氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AMPA)是谷氨酸的离子型跨膜受体。已报道AMPA受体阻滞剂可预防神经损伤并增强大鼠中风后恢复。癸酸,一种中链脂肪酸,已报道显示非竞争性AMPA受体拮抗作用。本研究评估了癸酸在缺血再灌注损伤前后对大鼠神经损伤和中风后恢复的影响。
方法:采用腔内方法诱发局灶性脑缺血进行大脑中动脉闭塞(MCAo)。一组口服癸酸(120mg/kg)1天(再灌注后5-10分钟),另一组口服2天(再灌注前24小时和再灌注后5-10分钟)。通过神经行为参数评估对神经损伤和卒中后恢复的影响,MRI和TTC染色以及炎症,氧化,凋亡,和神经保护生物标志物。
结果:癸酸可显著降低MCAo引起的神经损伤和梗死面积。癸酸处理增加了运动协调和握力。此外,炎症水平(TNFα,IL-1β和IL-6),氧化应激(MDA),癸酸治疗后,凋亡(TUNEL阳性细胞)和神经损伤(GFAP)生物标志物减少。发现抗炎细胞因子(IL-10)和神经保护标记(NT-3、BDNF和TrkB)随着癸酸处理而显著增加。
结论:本研究显示癸酸对大鼠缺血再灌注损伤的保护作用。抗炎,抗氧化剂,神经保护,和抗凋亡特性可能是研究中观察到的癸酸的有益作用的原因。
OBJECTIVE: Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) is an ionotropic transmembrane receptor for glutamate. AMPA receptor blockers have been reported to prevent neurological damage and enhance the post stroke recovery in rats. Decanoic acid, a medium-chain fatty acid, has been reported to exhibit non-competitive AMPA receptor antagonism. This study evaluated the effect of decanoic acid administered before and after ischemia reperfusion injury on neurological damage and post stroke recovery in rats.
METHODS: Middle cerebral artery occlusion (MCAo) was performed by using the intraluminal method to induce focal cerebral ischemia. Decanoic acid (120 mg/kg) was administered orally for 1 day (5-10 min post reperfusion) in one group and for 2 days (24 h pre and 5-10 min post reperfusion) in the other group. Effect on neurological damage and post stroke recovery was assessed by neurobehavioral parameters, MRI and TTC staining along with inflammatory, oxidative, apoptotic, and neuroprotective biomarkers.
RESULTS: Decanoic acid significantly reduced the MCAo induced neurological damage and infarct size. Decanoic acid treatment increased the motor coordination and grip strength. Furthermore, levels of inflammatory (TNFα, IL-1β and IL-6), oxidative stress (MDA), apoptotic (TUNEL positive cells) and neurological injury (GFAP) biomarkers were reduced after decanoic acid treatment. Anti-inflammatory cytokine (IL-10) and neuroprotective markers (NT-3, BDNF and TrkB) were found to be significantly increased with decanoic acid treatment.
CONCLUSIONS: This study showed protective effects of decanoic acid against ischemia reperfusion injury in rats. Anti-inflammatory, antioxidant, neuroprotective, and anti-apoptotic properties may be responsible for the beneficial effects of decanoic acid observed in the study.