Xu Huiqin, Ou Fuyong, Wang Pei, Naren Mangdula, Tu Dongpei, Zheng Rongyuan
Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
Department of Neurology, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan 423000, P.R. China.
Exp Ther Med. 2014 Jul;8(1):73-78. doi: 10.3892/etm.2014.1711. Epub 2014 May 14.
The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. To generate chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40 and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg) for 28 consecutive days. Epileptic behavior was observed using behavioral measurements of convulsion for 1 h after each treatment with pentylenetetrazole. Morphological alterations of the hippocampal neurons were also observed using hematoxylin and eosin staining. In addition, the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus were detected by immunohistochemistry. Furthermore, reverse transcription polymerase chain reaction was performed to detect the mRNA expression of two subunits (NR1 and NR2B) of the N-methyl-D-aspartic acid (NMDA) receptor in the rat hippocampus. The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an anticonvulsive effect in chronic epilepsy.
本研究的目的是探讨不同剂量胍丁胺对慢性癫痫大鼠作用的潜在机制。为建立慢性癫痫模型，用不同剂量胍丁胺（20、40和80mg/kg）预处理的大鼠连续28天腹腔注射戊四氮（35mg/kg）。每次注射戊四氮后1小时，通过惊厥行为测量观察癫痫行为。还用苏木精-伊红染色观察海马神经元的形态学改变。此外，通过免疫组织化学检测海马中胶质纤维酸性蛋白和诱导型一氧化氮合酶（iNOS）的表达水平。进一步地，进行逆转录聚合酶链反应以检测大鼠海马中N-甲基-D-天冬氨酸（NMDA）受体两个亚基（NR1和NR2B）的mRNA表达。结果表明，给予胍丁胺（80mg/kg）可显著降低癫痫发作的每日平均等级，还可减少海马区的神经元丢失和星形胶质细胞增生。此外，胍丁胺（80mg/kg）影响NMDA受体NR1亚基的mRNA表达水平，然而，胍丁胺对海马中iNOS的表达没有影响。较高剂量的胍丁胺抑制戊四氮对大鼠的作用，减少癫痫发作引起的海马星形胶质细胞增生和神经元损伤，并选择性降低NMDA的NR1亚基的表达。我们的结果表明，胍丁胺在慢性癫痫中具有抗惊厥作用。
