| Objective:The aims of the present study are to observe the effect of gastrodin on the behavior of epileptic rats,and to clarify the regulation of gastrodin of mitochondrial calcium Monoporter(MCU)and Caspase-3 in hippocampus by constructing the kindling model of chronic epilepsy rats induced by pentylenetetrazole(PTZ).Moreover,we tend to explore the therapeutic effect of gastrodin on epilepsy and to explain the possible mechanism.Methods:Thirty-three male SD rats,were randomly divided into 3 groups:normal control group(NC group),epilepsy model group(EP group)and gastrodin intervention group(GA group).To construct kindled model,EP group and GA group was intraperitoneal injection by subconvulsive dose of PTZ(35mg/kg).Post 60 minutes of PTZ injection,GA group was injected by gastrodin(6.0mg/kg),and EP group and NC group received the same dose of normal saline as GA group.All the injections were administrated at a specific time period each day,and the seizure intensity,seizure latency,seizure duration and death rate were continuously observed and recorded for 1 hour after injection.The hippocampus of rats were collected post 28 days of administration,and then the samples were stored in a-70? refrigerator after a rapidly frozen with liquid nitrogen.Western blot(WB)was used to detect the protein expression of MCU and Caspase-3 in hippocampus.Results:(1)Behavioral observation:the NC group did not appear epilepsy seizures;the successful rate of modeling in EP group was 72.73%,at 5 days post PTZ administration,36.36%of EP group was found to have a 1-4 grade epilepsy seizures,and the severe seizures period occurred at 14-28 days post injection;the successful rate of modeling in GA group was 72.73%,at 9 days post PTZ administration and gastrodin intervention,45.45%of GA group was found to have a 1-3 grade epilepsy seizures,and the severe seizure period occurred at 20-28 days post injection.Both EP group and GA group reached the kindling standard at 14 days post administration with more than five consecutive attacks of 1-4 grade epilepsy seizures,and the symptoms are characterized by frequent blinking,whisker beating,rhythmic nodding,face and limbs twitching,even falling,bouncing and body tonic spasm.(2)latent period,duration and intensity of epilepsy seizures:the NC group did not appear epilepsy seizures;compared with EP group,the GA group has shown prolonged latent period(P<0.05),a reduced duration of seizures(P<0.05),and a decreased seizures grade(P<0.05),these result give evidence that the situation of seizures after gastrodin intervention was significantly improved.(3)Expression of MCU and caspase-3 in hippocampus:there was significant difference in the relative protein expression of MCU and caspase-3 among the three groups(P<0.05).Compared with NC group,the expression of MCU and Caspase-3 in EP group was increased significantly(P<0.05);and compared with EP group,the expression of MCU and Caspase-3 in GA group was decreased significantly(P<0.05).Conclusions:(1)Continuous and periodic intraperitoneal injection of subconvulsive dose PTZ(35mg/kg)can successfully induce chronic epilepsy model in rats,which is characterized with a stable seizure and a low death rate.(2)Intraperitoneal injection of gastrodin intervention(6mg/kg)can alleviate and control the seizures of chronic epilepsy model in rats.(3)The expression of MCU and Caspase-3 in hippocampus is significantly increased post PTZ administration.(4)Treatment of gastrodin can significantly reducing the expression of MCU and caspases-3 in the hippocampus.(5)Gastrodin may exert an antagonize epilepsy effect by downregulate the expression of MCU and caspase-3. |
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