The Effects Of Ethyl Pyruvate On Neuronal Apoptosis And The Expression Of XIAP And Caspase-3 In Rats With Status Epilepticus

Objective: Ethyl pyruvate is a new type of brain protective agent. Reports have suggested that ethyl pyruvate can reduce the brain injury after Acute Global Cerebral Ischemia/Reperfusion, so as to protect the cerebral.However, the protective effection of Penehyclidine on brain damage which is led by status epilepticus( SE) have not been reported. In this research, after ethyl pyruvate pretreatment, the rats abdominal cavity are injected lithium-pilecarpine to make status epilepticus model. Observe the expression of apoptosis related genes Caspase-3,XIAP in rats hippocampus at different time points after SE, and compare it with anisodamine, discuss the effect of ethyl pyruvate intervention on neuronal damage after SE and its possible mechanism, with a view to ethyl pyruvate used in clinical treatment of SE to provide a possible basis for animal experiments.Methods: 54 healthy adult male Wistar rats were randomly divided into control group(n = 6 rats), model group(n = 24 rats), ethyl pyruvate group(n = 24 rats), the last two groups were divided into four sub-groups which are used at 6 hours, 12 hours, 24 hours, 48 hours after status epilepticus, each sub-group has 6 rats. The rats abdominal cavity of ethyl pyruvate group were injected ethyl pyruvate (50mg/kg) before 15 minutes ahead of making model. The control group were injected the same amount of saline at the corresponding time points. After 15 minutes, the model group and ethyl pyruvate group were given intraperitoneal injection of lithium chloride according to (127mg/kg). After 18 hours,the two groups were injected fresh pilocarpine (30mg/kg), making the model of status epilepticus.At the same time, the control group were injected the same amount of saline. Observe the performance and time when seizures rats appears . Model control group and ethyl pyruvate t group rats were sacrificed, respectively, at 6h, 12h, 24h, 48h after SE. The control group rats were killed together with rats that were sacrificed 6h after SE .then do some research on hippocampus. After HE staining, observe morphological changes under light microscope. Using the method of TUNEL to detect the apoptosis of rat hippocampal neurons, and immunohistochemical staining was used to test the expression of XIAP and Caspase-3. SPSS 13.0 version was used for statistical analysis and P<0.05 was considered statistically significant.Results: The positive cells of Caspase-3 ,XIAP and TUNEL in the control group only have a little basal expression. The expression of Caspase-3 , XIAP and TUNEL positive cells of hippocampus in the model group and ethyl pyruvate group is increasing after 6h of status epilepticus , Caspase-3 and TUNEL expression peaks are at 24h; XIAP expression reached its peak at 12h. Caspase-3 and TUNEL positive cells in ethyl pyruvate group were significantly reduced compared with model group (except for 6h, P <0.05), at different time points ,while the XIAP positive cells was significantly increased (except for 6h, P <0.05).Conclusion: (1) After status epilepticus, the protein expression of XIAP and Caspase-3 changes, confirmed that the two kinds of protein involved in the neuronal injury after status epilepticus. (2) The intervention of ethyl pyruvate can mitigate brain damage after status epilepticus by increasing the expression of XIAP and reducing the expression of Caspase-3. (3) The protective role of ethyl pyruvate against post-status epilepticus neuronal damage in rat is related with the mechanism effect of anti-apoptosis.