Status epilepticus (SE) leads to irreversible neuronal damage and consists of a complex pathogenesis that involves oxidative stress and subsequent autophagy. Rosiglitazone has recently been considered as a potential neuroprotective factor in epilepsy because of its antioxidative function. The aim of this study was to assess the effects of rosiglitazone in SE rat models and investigate whether its mechanisms of action involve autophagy via the antioxidant factor, nuclear factor erythroid 2-related factor 2 (Nrf2). The male Sprague-Dawley rats (200–220 g) were used to establish lithium-pilocarpine-induced SE model. We found that rosiglitazone markedly improved neuronal survival at 24-h post-SE as indicated via hematoxylin-eosin and Nissl staining. Furthermore, along with a reduction in reactive oxygen species, rosiglitazone pretreatment enhanced the antioxidative activity of superoxide dismutase and the expression level of Nrf2, as detected via chemical assay kits and Western blotting, respectively. In addition, the microtubule-associated protein light chain 3II (LC3II)/LC3I ratio was increased and peaked at 24 h after SE, whereas p62 mRNA levels were sharply elevated at 72 h after SE, both SE-induced increases of which were reversed via rosiglitazone pretreatment. To further test our hypothesis of the key role of Nrf2 in this process, small-interfering RNA for Nrf2 (siNrf2) was then transfected into SE rats to knockdown Nrf2 expression. We found that siNrf2 partially blocked the above effects of rosiglitazone on autophagy-related proteins in SE rats. Taken together, our findings suggest that rosiglitazone attenuates oxidative-stress-induced autophagy via increasing Nrf2 in SE rats and may be used as a promising therapeutic strategy for SE treatment.

癫痫持续状态（SE）导致不可逆的神经元损害，由复杂的发病机制组成，涉及氧化应激和随后的自噬。罗格列酮由于其抗氧化功能，最近被认为是癫痫的潜在神经保护因子。这项研究的目的是评估罗格列酮在SE大鼠模型中的作用，并研究其作用机制是否通过抗氧化因子，核因子类红细胞2相关因子2（Nrf2）参与自噬。使用雄性Sprague-Dawley大鼠（200–220 g）建立锂-毛果芸香碱诱发的SE模型。我们发现罗格列酮显着改善了SE后24小时的神经元存活，如苏木精-伊红和Nissl染色所示。此外，随着活性氧种类的减少，罗格列酮预处理分别通过化学分析试剂盒和Western blotting检测可增强超氧化物歧化酶的抗氧化活性和Nrf2的表达水平。此外，微管相关蛋白轻链3II（LC3II）/ LC3I的比例在SE后24 h增加并达到峰值，而p62 mRNA水平在SE后72 h急剧升高，这两种SE诱导的增加均通过罗格列酮预处理。为了进一步检验我们对Nrf2在这一过程中的关键作用的假设，然后将Nrf2的小干扰RNA（siNrf2）转染到SE大鼠中以敲低Nrf2的表达。我们发现siNrf2部分阻断了罗格列酮对SE大鼠自噬相关蛋白的上述作用。在一起