Noori Tayebeh, Dehpour Ahmad Reza, Alavi Seyede Darya, Hosseini Seyede Zahra, Korani Sina, Sureda Antoni, Esmaeili Jamileh, Shirooie Samira
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2023;26(11):1272-1282. doi: 10.22038/IJBMS.2023.71309.15493.
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) and its cause is unknown. Several environmental and genetic factors may have roles in the pathogenesis of MS. The synthesis of solid lipid nanoparticles (SLNs) for ivermectin (IVM) loading was performed to increase its efficiency and bioavailability and evaluate its ability in improving the behavioral and histopathological changes induced by cuprizone (CPZ) in the male C57BL/6 mice.
Four groups of 7 adult C57BL/6 mice including control (normal diet), CPZ, IVM, and nano-IVM groups were chosen. After synthesis of nano-ivermectin, demyelination was induced by adding 0.2% CPZ to animal feed for 6 weeks. IVM and nano-IVM (1 mg/kg/day, IP) were given for the final 14 days of the study. At last, behavioral tests, histochemical assays, and immunohistochemistry of TRPA1, NF-kB p65, and GFAP were done.
The time of immobility of mice in the IVM and nano-IVM groups was reduced compared to the CPZ group. Histopathological examination revealed demyelination in the CPZ group, which was ameliorated by IVM and nano-IVM administration. In IVM and nano-IVM groups corpus callosum levels of TRPA1, NF-kB p65, and GFAP were decreased compared to the CPZ group. In the IVM and nano-IVM groups, the levels of MBP were significantly higher than in the CPZ group.
The results evidenced that IVM and nano-IVM administration is capable of reducing demyelination in mice.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性疾病，其病因不明。多种环境和遗传因素可能在MS的发病机制中起作用。进行了用于负载伊维菌素（IVM）的固体脂质纳米粒（SLN）的合成，以提高其效率和生物利用度，并评估其改善由铜离子载体（CPZ）诱导的雄性C57BL/6小鼠行为和组织病理学变化的能力。
选取四组，每组7只成年C57BL/6小鼠，包括对照组（正常饮食）、CPZ组、IVM组和纳米IVM组。纳米伊维菌素合成后，通过在动物饲料中添加0.2% CPZ诱导脱髓鞘6周。在研究的最后14天给予IVM和纳米IVM（1 mg/kg/天，腹腔注射）。最后，进行行为测试、组织化学分析以及TRPA1、NF-κB p65和GFAP的免疫组织化学检测。
与CPZ组相比，IVM组和纳米IVM组小鼠的不动时间减少。组织病理学检查显示CPZ组存在脱髓鞘，IVM和纳米IVM给药可改善这种情况。与CPZ组相比，IVM组和纳米IVM组胼胝体中TRPA1、NF-κB p65和GFAP的水平降低。在IVM组和纳米IVM组中，髓鞘碱性蛋白（MBP）水平显著高于CPZ组。
结果证明给予IVM和纳米IVM能够减少小鼠的脱髓鞘。
