Abstract：
Temporal lobe epilepsy (TLE) leads to extensive degradation of the quality of life of patients. Glycyrrhizic acid (GA) has been reported to exert neuroprotective effects on status epilepticus. Herein, the current study set out to explore the functional mechanism of GA in TLE young rats. Firstly, TLE young rat models were established using the lithium chloride and pilocarpine regimen and then subjected to treatment with different doses of GA, miR-194-5p-antagomir, or/and sh-prostaglandin-endoperoxide synthase 2 (PTGS2) to observe changes in iron content, glutathione and malondialdehyde levels, and GPX4 (glutathione peroxidase 4) and PTGS2 protein levels in the hippocampus. Neuronal injury and apoptosis were assessed through HE, Nissl, and TUNEL staining. Additionally, the expression patterns of miR-194-5p were detected. The binding site of miR-194-5p and PTGS2 was verified with a dual-luciferase assay. Briefly, different doses of GA (20, 40, and 60 mg/kg) reduced the epileptic score, frequency, and duration in TLE young rats, along with reductions in iron content, lipid peroxidation, neuronal injury, and apoptosis in the hippocampus. Silencing of miR-194-5p partly annulled the action of GA on inhibiting ferroptosis and attenuating neuronal injury in TLE young rats. Additionally, PTGS2 was validated as a target of miR-194-5p. GA inhibited ferroptosis and ameliorated neuronal injury in TLE young rats via the miR-194-5p/PTGS2 axis. Overall, our findings indicated that GA exerts protective effects on TLE young rats against neuronal injury by inhibiting ferroptosis through the miR-194-5p/PTGS2 axis.
摘要：
颞叶癫痫（TLE）导致患者生活质量的广泛下降。据报道，甘草酸（GA）对癫痫持续状态具有神经保护作用。在这里，本研究旨在探讨GA在TLE幼鼠中的作用机制。首先,使用氯化锂和毛果芸香碱方案建立TLE幼鼠模型，然后用不同剂量的GA进行治疗，miR-194-5p-antagomir,或/和SH-前列腺素-内过氧化物合酶2（PTGS2）观察铁含量的变化，谷胱甘肽和丙二醛水平，海马中的GPX4（谷胱甘肽过氧化物酶4）和PTGS2蛋白水平。通过HE评估神经元损伤和凋亡，Nissl,和TUNEL染色。此外,检测到miR-194-5p的表达模式。miR-194-5p和PTGS2的结合位点用双荧光素酶测定来验证。简而言之，不同剂量的GA（20、40和60mg/kg）降低了癫痫评分，频率,和TLE幼鼠的持续时间，随着铁含量的减少，脂质过氧化，神经元损伤，和海马细胞凋亡。miR-194-5p的沉默部分消除了GA抑制TLE幼鼠铁凋亡和减轻神经元损伤的作用。此外,PTGS2被验证为miR-194-5p的靶标。GA通过miR-194-5p/PTGS2轴抑制TLE幼鼠铁凋亡并改善神经元损伤。总的来说,我们的研究结果表明,GA通过miR-194-5p/PTGS2轴抑制铁性凋亡,对TLE幼鼠的神经元损伤具有保护作用.
