| Oxcarbazepine is a novel antiepileptic drug, is10-ketone derivative of carbamazepine, suitable for complex partial seizure, separate treatment of generalized tonic-clonic seizures and adjuvant treatment of patients with refractory epilepsy. With rapid oral absorption, high bioavailability, few side-effects, more and more emphasis on the clinical. The mechanisms may be:①inhibiting voltage-dependent sodium channel of continuous, repeated, high frequency discharge,reducing the content of intracellular cAMP, increasing5-hydroxytryptamine,reducing the excitability of neurons and enhancing cell stability.②inhibiting high voltage activated n-type and p-type calcium channels, reducing the release of the excitatory neurotransmitter glutamate and lower epileptic seizures.Saber assessed newly diagnosed patients that received OXC or other AEDs as a monotherapy for4months,compared with baseline, Oxcarbazepine in intelligence, memory, language, attention, and learning vision were not damaged, Oxcarbazepine and carbamazepine groups, the ability of learning and memory has improved. Other scholars had a double-blind design, to study the influence of memory, attention and psychomotor speed of Oxcarbazepine, and found that Oxcarbazepine without obvious influence on cognitive function. For evaluate the effects of Oxcarbazepine on cognitive function scientificly, used the rats with pentylenetetrazol-induced epilepsy model, evaluating Oxcarbazepine on change of cognitive function by water maze.Seizures can cause nerve cell injury, recently more and more experiments showed that cells apoptosis made an important role in seizure-induced brain injury. Caspase protein is a class-specific cysteine aspartic acid protease, is the execution of apoptosis, the core enzyme of Caspase-3appears as a sign of cell apoptosis.NO is a short life production that catalyzed by nitric oxide synthase (NOS), the nature is very lively, played an important and complex role in the central nervous system. Some scholars believe that epilepsy casue by NOS is not dependent on calcium of inducible nitric oxide synthase, excessive NO causes apoptosis.The topic by intraperitoneal injection to rat to make epilepsy model by pentylenetetrazole, give Oxcarbazepine intervention, through the Morris water maze to test every groups learning and memory ability. And through immunohistochemistry technique to observe the expression of induced nitric oxide synthase (iNOS) and Caspase-3at different time after seizures. Combining behavioral tests and tissue pathological examination study, to study the neuroprotective effect of Oxcarbazepine, to provide reference foundation for preventing seizure-induced neuronal damage.Objective To investigate oxcarbazepine(OXC)the sheltering effects of cognitive function and the correlation and dynamic changes of protein expression of Inos and Caspase-3in epileptic rats by pentrilone(PTZ).Methods Fifty-two healthy Wistar rats were randomly divided into four groups: Group A is physiological saline(NS)group, group B is epilepsy(EP)+NS group, group C is EP+OXC group, group D is OXC group. Group B、C were made by intraperitoneal injection of pentylenetetrazole60mg/kg-1, according to Racine classification, the epileptic models were successfully constructed through5consecutive days of Ⅳ-Ⅴ level attacks, each attack lasting3-5minutes. On the6th day, group A and group B were given saline by gavage,group C and group D were given OXC by gavage. Each group randomly taken8rats, they are classed into Immunocytochemistry subgroup. After continuous medication for6hours,3days,7days,12days,rats were respectively killed and the brain were removed, they were observed the morphological changes of apoptosis cells and number changes by immunohistochemical staining, the rest of rats were Water maze subgroup, they conducted the Water maze test after continuous medication for3to6days,9to12 days, we will observe the change of their spatial cognition and conditional learning and memory abilities.Results1.the experimental groups were given intraperitoneal injection with pentylenetetrazole,all appeared epileptic seizures. the success rate of100%, and died5, mortality9.6%.2. The Morris water maze testPlace navigation test:The first phase test(taking medicine3-5days) The latent period finding the flat of EP+NS group is longer than NS group and the difference is notable(P<0.05); The latent period finding the flat of EP+OXC group is longer than NS group in the third day and the difference is notable(P<0.05); The latent period finding the flat of EP+OXC group is shorter than NS group in the fifth day and the difference is notable(P<0.05); The latent period finding the flat of EP+OXC group is shorter than NS group in the fourth and fifth day, and the difference is notable(P<0.05);The second phase test(taking medicine9～11days) The latent period finding the flat of EP+NS group is longer than NS group and the difference is notable(P<0.05); The latent period finding the flat of EP+OXC group is longer than NS group in the ninth and tenth days, the difference is notable(P<0.05),and compared with EP+NS group, The latent period finding the flat of EP+NS group is shorter and the the difference is notable(P<0.05).Spatial probe test:Crossing the platform number of each group:Crossing the platform number in EP+NS group is fewer than NS group, the difference is notable(P<0.05);Compared EP+OXC group and EP+NS group, there is no significant differences in the number of crossing platform (P>0.05).3. immunohistochemical stainingiNOS immune reaction product is Brown, and mainly located in neuron caryoplasm.And Caspase-3mainly located in neuron caryoplasm,is brown yellow.The expression of iNOS in EP+NS group is mult compare with other groups,iNOS expression in a time-depend manner,6h,3d,7d groups increased significantly,with6h is most significant; The expression of Caspase-3in EP+NS group is mult,Caspase-3expression in a time-depend manner,6h,3d,7d groups increased significantly,with7d is most significant.4. positive immunohistochemical reaction product the average optical densityCompared with NS group, the average optical density of Caspase-3in iNOS and OXC groups are no differences(P>0.05), the average optical density of Caspase-3in EP+NS group is notable (P<0.01),the average optical density of iNOS in EP+NS group at6h,3D,7d is notable(P<0.01); Compared with EP+NS group,the average optical density of Caspase-3in EP+OXC group (at7d,12d) is notable(P<0.01), EP+OXC group of iNOS average optical density (at3d,7d,12d) is notable(P<0.01).Conclusions OXC has a clear anti-epilepsy effect and protective effect on cognitive function, its possible mechanism is to reduce the expression of iNOS and Caspase-3; OXC does not affect normal mice’s cognitive function。... |
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