关键词: 癫痫；线粒体ATP敏感性钾通道；二氮嗪；超微结构；自由基；大鼠，Wistar

Abstract:

Objective    To observe the effect of diazoxide(DZ), a mitochondrial ATPsensitive potassium channel (mitoKATP) opener, on neuronal ultrastructure and free radicals in the hippocampus of epileptic rats induced by lithium-pilocarpine, and explore the mechanism of the neuroprotective effect of DZ on epilepsy. Methods    Adult male Wistar rats were randomly divided into four groups: the control group, the epilepsy group (PILO group), the diazoxide group (DZ group), and the DZ and 5-hydroxydecanoate(5-HD) group (DZ+5-HD group). The model of status epilepticus (SE) was induced by lithium-pilocarpine. Before preparation of the model, the DZ group was treated with 5mg/kg of DZ, intraperitoneally injected (ip); and the DZ+5-HD group was treated with 8mg/kg of 5-HD, ip, then 5mg/kg of DZ, ip. The change of behavior in rats was observed. 4, 24 and 48 hours after SE, the rats were sacrificed and the hippocampi were removed. The neuronal ultrastructure was observed by an electron microscope. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured with commercial assay kits. Results    Compared with the control group, hippocampal neurons in the PILO group and the DZ+5-HD group were severely damaged after SE. The number of neurons was decreased, and the neurons were swellen. There were numerous clumps distributed throughout the nucleus. Mitochondrial swelling was accompanied by the disappearance of cristae and disruption of membrane integrity. In more severe cases, the mitochondria were vacuolar. The damage was most severe 48h after SE. In the DZ group, the epileptic paroxysm latent period was significantly prolonged, the damage of neurons was less severe, and the mortality rate of rats with SE was decreased. In the DZ group, the MDA content was significantly decreased while the activities of SOD and GSH-Px were significantly increased compared with those in the PILO group. The effect of DZ could be abolished by 5-HD. Conclusion    The mitoKATP opener DZ can decrease the level of mitochondrial free radicals, thereby improve the response of the anti-oxidant system, and reduce oxidative stress after SE, so it can reduce neuronal injury and play an important role in neuroprotection after SE.  

Key words: Epilepsy; Mitochondrial ATP-sensitive potassium channel; Diazoxide; Ultrastructure; Free radicals; Rats，Wistar