Soleimani Pouria, Nekoonam Saied, Zafari Fariba, Sabbaghziarani Fatemeh
Student Research Committee, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
IBRO Neurosci Rep. 2025 Jun 10;19:83-90. doi: 10.1016/j.ibneur.2025.06.004. eCollection 2025 Dec.
Stroke is the second leading cause of death and long-term damage globally. Inflammation is a significant factor in the onset of ischemic stroke. This study investigated the simultaneous administration of melatonin and N-acetylcysteine (NAC) on inflammation in rat cerebral ischemia. First, 30 male Wistar rats were randomly divided into five groups (n = 6), including the sham group without ischemia, the ischemic group, and the ischemic groups treated with NAC, melatonin, and NAC + melatonin, respectively. To induce ischemia, a silicone-coated monofilament was placed from the common carotid artery towards the middle cerebral artery and stained for 60 min. The rats were treated by administering NAC (50 mg/kg), melatonin (5 mg/kg) and the combination of NAC + melatonin by intraperitoneal injection after ischemia induction. The animals were assessed for sensory-motor activity at 24 and 72 h. Following sacrifice, the rats' brain was dissected to estimate infarct volume after triphenyltetrazolium chloride (TTC) staining. Inflammatory parameters were then analyzed through gene expression analysis using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and nucleotide oligomerization domain (NOD)-like receptor family with pyrin domain 1 and 3 (NLRP1 and NLRP3). The results showed a significant decrease in mRNA expression of the target genes in the rats treated with NAC + melatonin compared to the ischemic group (p < 0.05). The group that received the combined treatment exhibited enhanced sensory-motor function and a reduced brain infarct volume compared to the other groups (p < 0.05). In summary, the combined use of NAC and melatonin has shown promise in enhancing neurobehavioral function and decreasing the volume of cerebral infarction by regulating the inflammatory signaling pathway.
中风是全球第二大致死和长期损伤的原因。炎症是缺血性中风发病的一个重要因素。本研究调查了褪黑素和N-乙酰半胱氨酸（NAC）联合给药对大鼠脑缺血炎症的影响。首先，将30只雄性Wistar大鼠随机分为五组（n = 6），包括无缺血的假手术组、缺血组，以及分别用NAC、褪黑素和NAC + 褪黑素治疗的缺血组。为诱导缺血，将一根硅胶涂层单丝从颈总动脉插入大脑中动脉并阻塞60分钟。缺血诱导后，通过腹腔注射给予大鼠NAC（50 mg/kg）、褪黑素（5 mg/kg）以及NAC + 褪黑素组合进行治疗。在24小时和72小时评估动物的感觉运动活动。处死后，解剖大鼠大脑，经氯化三苯基四氮唑（TTC）染色后估计梗死体积。然后通过逆转录定量聚合酶链反应（RT-qPCR）对核因子κB（NF-κB）、肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）以及含吡啉结构域的NOD样受体家族成员1和3（NLRP1和NLRP3）进行基因表达分析，以分析炎症参数。结果显示，与缺血组相比，NAC + 褪黑素治疗的大鼠中靶基因的mRNA表达显著降低（p < 0.05）。与其他组相比，接受联合治疗的组表现出增强的感觉运动功能和减小的脑梗死体积（p < 0.05）。总之，NAC和褪黑素联合使用在通过调节炎症信号通路增强神经行为功能和减少脑梗死体积方面显示出前景。
