DPP4 regulates the inflammatory response in a rat model of febrile seizures
DPP4 regulates the inflammatory response in a rat model of febrile seizures
复制标题
DPP4 调节热性惊厥大鼠模型的炎症反应
DOI：
10.3233/bme-171635
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发表时间：
2017-01-01
影响因子：
1
通讯作者：
He, Xiaohua
中科院分区：
文献类型：
--
作者：
Sun, Qi;Zhang, Yusong;He, Xiaohua
热性惊厥 (FS) 是 6 个月至 5 岁儿童中最常见的癫痫症。患有复杂 FS 的儿童随后发生颞叶癫痫 (TLE) 的风险很高。神经炎症参与 FS 的发病机制，但其机制仍不清楚。我们之前使用大鼠全基因组寡芯片的研究确定二肽基肽酶 IV (DPP4) 可能是 FS 大鼠的相关基因。在这项研究中，我们证明了热诱导后 DPP4 的蛋白质和 mRNA 水平表达均显着增加。西他列汀是 DPP4 的一种特异性酶抑制剂，可显着减轻 FS 大鼠癫痫发作的严重程度，并且在抑制 DPP4 后，高热诱导的星形细胞增多症也受到抑制。此外，西他列汀显着降低炎症细胞因子 IL-1β、TNF-α 和 IL-6 的水平，但不降低 IL-10。此外，西格列汀通过降低 p65 亚基的磷酸化来防止 NF-κ B 激活。综上所述，我们的研究结果表明，DPP4 在高热诱发的癫痫发作中作为神经炎症的关键调节因子发挥作用，并且 DPP4 抑制剂可能是 FS 治疗的可行选择。
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction. Sitagliptin, a specific enzyme inhibitor of DPP4, remarkably attenuated the severity of seizures in FS rats, and hyperthermia-induced astrocytosis was suppressed after DPP4 inhibition. Furthermore, sitagliptin significantly decreased the levels of the inflammatory cytokines IL-1 beta, TNF-alpha, and IL-6 but not IL-10. In addition, sitagliptin prevented NF-kappa B activation by decreasing phosphorylation of the p65 subunit. Taken together, our findings demonstrate that DPP4 functions as a critical regulator of neuroinflammation in hyperthermia-induced seizures and the DPP4 inhibitor may be a viable option for FS therapeutics.