Wang Aihua, Si Zhihua, Li Xiaolin, Lu Lu, Pan Yongli, Liu Jinzhi
Department of Neurology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated With Shandong First Medical University, Jinan, China.
Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Front Neurol. 2019 Sep 12;10:971. doi: 10.3389/fneur.2019.00971. eCollection 2019.
The status epilepticus (SE) is accompanied by a local inflammatory response and many oxygen free radicals. FK506 is an effective immunosuppressive agent with neuroprotective and neurotrophic effects, however, whether it can inhibit the inflammatory response and attenuate epilepsy remains unclear. This study aims to clarify the effect of FK506 on inflammatory response in rats with epilepsy. A total of 180 rats were randomly and equally divided into the control group, epilepsy group, and FK506 group. The rat SE model in the epilepsy group and FK506 group was induced by lithium chloride combined with pilocarpine. In the FK506 group, FK506 was given before the injection of pilocarpine. The control group was given the same volume of saline. Then the effect of FK506 on epilepsy in rats and the changes of inflammatory factors and free radicals in hippocampus were examined using hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. FK506 ameliorated the course of pilocarpine-induced epilepsy and the neuronal loss in the rat hippocampus after SE. FK506 reduced the increased content of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the hippocampus after SE. Besides, FK506 also significantly reduced the levels of factors involved in inflammatory response such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and Protein Kinase C δ (PKCδ) that rise after epilepsy. FK506 ameliorated the course of pilocarpine-induced epilepsy, significantly reduced free radical content, and inhibited the expression of inflammatory factors, which provided a theoretical basis for the application of FK506 in the treatment of epilepsy.
癫痫持续状态（SE）伴有局部炎症反应和大量氧自由基。FK506是一种具有神经保护和神经营养作用的有效免疫抑制剂，然而，它是否能抑制炎症反应并减轻癫痫尚不清楚。本研究旨在阐明FK506对癫痫大鼠炎症反应的影响。总共180只大鼠被随机等分为对照组、癫痫组和FK506组。癫痫组和FK506组的大鼠SE模型通过氯化锂联合毛果芸香碱诱导。在FK506组中，在注射毛果芸香碱前给予FK506。对照组给予相同体积的生理盐水。然后使用苏木精-伊红（HE）染色、免疫组织化学、定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法检测FK506对大鼠癫痫的影响以及海马中炎症因子和自由基的变化。FK506改善了毛果芸香碱诱导的癫痫病程以及SE后大鼠海马中的神经元丢失。FK506降低了SE后海马中一氧化氮（NO）、超氧化物歧化酶（SOD）和丙二醛（MDA）含量的增加。此外，FK506还显著降低了癫痫后升高的炎症反应相关因子如血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）和蛋白激酶Cδ（PKCδ）的水平。FK506改善了毛果芸香碱诱导的癫痫病程，显著降低了自由基含量，并抑制了炎症因子的表达，这为FK506在癫痫治疗中的应用提供了理论依据。
