Hamamci Mehmet, Doganyigit Zuleyha, Silici Sibel, Okan Aslı, Kaymak Emin, Yilmaz Seher, Tokpinar Adem, Inan Levent Ertuğrul
Department of Neurology, Bozok University Medical School, Yozgat, Turkey.
Department of Histology-Embryology, Bozok University Medical School, Yozgat, Turkey.
Acta Neurol Taiwan. 2020 Jun 30;29(2):33-45.
This study was designed to investigate the effect of apilarnil on neuronal damage and related mechanisms in a sepsis model in order to demonstrate whether or not apilarnil has neuroprotective effect.
In this study, 64 adult male Sprague-Dawley species rats were randomly divided into eight groups. The rats were administered apilarnil and/or lipopolysaccharide (LPS). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), xanthine oxidase (XOD) and testican-1 levels were measured in the brain tissue. Proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], interleukin 6 [IL-6]) were measured in brain tissue. Histological examinations were performed on hippocampus and cortex tissues in all groups. Apoptotic cell count was estimated using the Tunel method to observe the apilarnil's effect on apoptosis. Purkinje cells were counted in the hippocampus to measure the protective effect of apilarnil on the hippocampus.
Apilarnil reduced the decrease in SOD and CAT levels in the brain developing sepsis. Apilarnil reduced the increase in MDA, XOD, and testican-1 levels in the septic brain. It was observed that the number of degenerated neurons due to sepsis decreased as apilarnil dose increased. Apilarnil reduced the elevated levels of proinflammatory cytokines (IL-6, TNF-α, IL-1β) induced by sepsis. Apilarnil prevented sepsis-related apoptosis in the brain.
The neuroprotective potential of apilarnil against brain damage in the sepsis model was demonstrated and suggested that it has the potential to contribute to new therapeutic targets against various neurological disorders.
本研究旨在探讨阿匹拉尼尔对脓毒症模型中神经元损伤的影响及相关机制,以证明阿匹拉尼尔是否具有神经保护作用。
本研究中,64只成年雄性Sprague-Dawley大鼠被随机分为八组。给大鼠施用阿匹拉尼尔和/或脂多糖(LPS)。测量脑组织中的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、黄嘌呤氧化酶(XOD)和睾丸抑制素-1水平。测量脑组织中的促炎细胞因子(肿瘤坏死因子α [TNF-α]、白细胞介素1β [IL-1β]、白细胞介素6 [IL-6])。对所有组的海马和皮质组织进行组织学检查。使用Tunel法估计凋亡细胞计数,以观察阿匹拉尼尔对细胞凋亡的影响。对海马中的浦肯野细胞进行计数,以测量阿匹拉尼尔对海马的保护作用。
阿匹拉尼尔减少了脓毒症发展过程中大脑中SOD和CAT水平的降低。阿匹拉尼尔降低了脓毒症大脑中MDA、XOD和睾丸抑制素-1水平的升高。观察到随着阿匹拉尼尔剂量增加,脓毒症导致的变性神经元数量减少。阿匹拉尼尔降低了脓毒症诱导的促炎细胞因子(IL-6、TNF-α、IL-1β)的升高水平。阿匹拉尼尔预防了大脑中与脓毒症相关的细胞凋亡。
证明了阿匹拉尼尔在脓毒症模型中对脑损伤具有神经保护潜力,并表明它有可能为针对各种神经系统疾病的新治疗靶点做出贡献。