A Study Of Neuroprotective Effect Of FPS-ZM1 And NGF On Brain Of PTZ Induced Epilepsy Young Rats

ObjectiveTo investigate the changes of HMGB1 and TRX in hippocampus and serum after seizures in rats with epilepsy induced by pentylenetetrazol,then used the RAGE receptor inhibitors FPS-ZM1 and neurotrophic factor mNGF to intervene,observed the effects of the two drugs on the expression of HMGB1 and TRX,then explored the brain tissue damage after seizure and the neuroprotective effects of FPS-ZM1 and mNGF,in order to provide a theoretical basis for clinical intervention,prevention and improvement of brain damage caused by epilepsy,and provided a new direction for clinical treatment of epilepsy.Methods130 clean level Wistar male rats(3-4 weeks,weight 50-60g)were randomly divided into group A(normal control group,n=31),group B(epilepsy group,n=33),group C(mNGF group,n=33),Group D(FPS-ZM1 group,n=33).Young rats were injected intraperitoneally with pentylenetetrazol 40mg/kg to establish a model of chronic ignited epilepsy.After successful modeling,groups A and B were given equal doses of normal saline,group C was given mNGF 2000 AU/kg,group D was given FPS-ZM1 1mg/kg by intraperitoneal injection for 1 week,and the behavioral performance was observed for 30 min after injection.After the intervention,the rats were anesthetized by intraperitoneal injection of pentobarbital at 3h,24 h and 72 h.The hippocampus was isolated after the trunk blood was taken.The expression level of HMGB1 in hippocampus was determined by Western-blot method,the content of serum HMGB1 and TRX in serum and hippocampus were detected by ELISA.Results1.Behavior of young rats: the rats in normal control group moved freely after normal saline injection,and there was no seizure behavior appeared,different degrees of seizures were occurred in rats with epilepsy after PTZ injection.With the extension of modeling time,the level of attack gradually increased,eventually reaching the standard of chronic ignition.2.The expression level of HMGB1 in the hippocampus of the epilepsy group was significantly higher than that of the normal control group at each time point,and the difference was statistically significant(P=0.00);The expression level of HMGB1 in FPS-ZM1 group and mNGF group were significantly lower than those in epilepsy group at each time period(P<0.05);The expression level of HMGB1 in FPS-ZM1 group was more obviously lower at 3h/24 h than that in mNGF group,the difference was statistically significant(P<0.05);And the difference between the two group was not statistically significant(P>0.05).The level of HMGB1 protein expression in serum was similarly resulted.3.The TRX content in the hippocampus of the epilepsy group was lower than that in the normal control group,and the difference was statistically significant(P<0.01);The TRX content in FPS-ZM1 group and mNGF group was higher than that in the epilepsy group at each time point,but it was lower than the normal control group,there was statistically significant difference(P<0.05);There was no significant difference in TRX content between the FPS-ZM1 group and the mNGF group at different time point(P>0.05).The TRX in serum also saw the same result.Conclusions1.The expression of HMGB1 protein was increased,and the content of TRX was decreased in young rats with epilepsy,suggested that immune inflammatory reaction and oxidative stress might involve in the process of epilepsy.2.Serum HMGB1 and TRX may be biochemical indicators reflecting brain damage after epilepsy.3.FPS-ZM1 and mNGF could protect against the early inflammatory reaction and oxidative stress damage in young rats with epilepsy.