Department of Pediatrics, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, PR China.
Experimental Center, School of Life Sciences, North China University of Science and Technology, Tangshan 063000, PR China.
Biomed Pharmacother. 2019 Jun;114:108683. doi: 10.1016/j.biopha.2019.108683. Epub 2019 Apr 1.
This study is conducted to explore the role of microRNA-223 (miR-223) in brain injury and apoptosis of hippocampal neurons through the NLRP3-Caspase-1 signaling pathway in febrile seizure (FS) rats.
The models of FS were induced in rats by hot water-bath, which were stereotactically injected with miR-223 mimics and mimics negative control (NC) to perturb the expression of miR-223. A series of experiments was conducted to find out the potential mechanisms of miR-223 on convulsion attack, learning and memory ability, pathological injury of hippocampal neurons, inflammatory injury, apoptosis of hippocampal neurons in FS rats. Besides, the targeting relationship between miR-223 and NLRP3 was also verified.
Low expression of miR-223 was found in hippocampus tissues of FS rats. Up-regulation of miR-223 alleviated convulsion attack and improved learning and memory ability, while inhibiting pathological injury of hippocampal neurons and inflammatory injury in FS rats. Up-regulation of miR-223 promoted the survival of hippocampal neurons and inhibited their apoptosis in FS rats. MiR-223 inhibited the activation of NLRP3-Caspase-1 signaling pathway in hippocampus tissues of FS rats by inhibiting NLRP3.
The inhibited expression of miR-223 after FS may participate in the activation of the NLRP3-Caspase-1 signaling pathway, resulting in brain injury and apoptosis of hippocampal neurons in rat models of FS.
本研究旨在通过 NLRP3-Caspase-1 信号通路探讨微小 RNA-223（miR-223）在热性惊厥（FS）大鼠脑损伤和海马神经元细胞凋亡中的作用。
采用热水浴法诱导 FS 大鼠模型，立体定向注射 miR-223 模拟物和模拟物阴性对照（NC）以干扰 miR-223 的表达。进行了一系列实验以研究 miR-223 对 FS 大鼠惊厥发作、学习记忆能力、海马神经元病理损伤、炎症损伤、海马神经元凋亡的潜在作用机制。此外，还验证了 miR-223 与 NLRP3 之间的靶向关系。
FS 大鼠海马组织中 miR-223 表达水平降低。上调 miR-223 可减轻 FS 大鼠的惊厥发作，改善学习记忆能力，同时抑制 FS 大鼠海马神经元的病理损伤和炎症损伤。上调 miR-223 可促进 FS 大鼠海马神经元的存活并抑制其凋亡。miR-223 通过抑制 NLRP3 抑制 FS 大鼠海马组织中 NLRP3-Caspase-1 信号通路的激活。
FS 后 miR-223 的表达抑制可能参与 NLRP3-Caspase-1 信号通路的激活，导致 FS 大鼠模型脑损伤和海马神经元细胞凋亡。
