| Objective: Epilepsy is a chronic neurological disorder with recurrent relapses and spontaneous hair as features.In adults temporal lobe epilepsy is the most common and most difficult.Patients with seizures relatedto brain structures such as the hippocampus still further damage problems,the damage will promote injury cognitive function. Now that the pathogenesis of epilepsy: the doctrine of excitatory amino acid toxicity,energy metabolism imbalance, calcium overload,oxidative stress,proinflammatory cytokines injury, apoptosis.After the seizure explore the mechanismof neuronal apoptosis revealed apoptosis signaling pathways.Bax is theBcl-2family member involved in apoptosis,induction of apoptosis whenit moved from the cytosol to the mitochondria and nuclear membrane.Bcl-2is a physiological function of apoptosis repressor prolong cell life.BDNF is a nerve in1982by the German chemist Barde, who first isolated and purified from porcine brain a protein can promote nerve growthactivity. BDNF acts on certain neurons in the central nervous system and peripheral nervous system,which helps to support the survival of existing neurons and encourage new neuronal and synaptic growth and differentiation.Seizures can cause nerve cell damage has been widely confirmed,there is still a lack of effective means of protection,so explore newneuroprotective agents have important clinical significance.Lipoic acid isa class B vitamins substances,lipoic acid exists in many foods rich inantioxidant alpha lipoic acid and within easy reach of the central nervous system through the blood-brain barrier by showing pharmacological value worthy of attention.LA has against apoptosis induced by oxidativestress.It is reported that lipoic acid can inhibit neuronal apoptosis in theaging process,improve cell survival. In view of this study, Male Wistar rats, basolateral application of nuclear power to ignite Act rat model of chronic epilepsy on the basis of these observations seizures recorded Racine grading the severity and duration;and give α-lipoic acid,observed intervention before and after theseverity and duration of seizures in rats, observe the behavior of each group of rats to learn,hippocampal tissue morphology,and the use of Western Blot, immunohistochemistry observed inhibition of apoptosis/promote protein Bcl-2/Bax,brain-derived of neurotrophic factors (brain derivedneurophic factor,BDNF) expression in the hippocampus tissues to studyα-lipoic acid in rats and neuroprotective effects of antiepileptic almonds ignite nuclear model of epilepsy, and explore its possible mechanism.Methods:The367-8weeks weighing250-300g clean adult male Wistar rats were randomly divided into groups:normal control group,shamoperation group,epilepsy group and the normal group lipoic acid,lipoic acid low dose electrical stimulation,electrical stimulation of sulfur bitterness of the high dose group,six rats in each group.Control group:rats dailyintraperitoneal injection of0.9%saline40mg/kg, drug injection in themorning between08:30-09:30every day,a total of15times. Sham group:amygdala implanted electrodes are not given electrical stimulation. Epilepsy Group:120%of the implanted electrodes by electrical stimulationseizure threshold once daily electrical stimulation15days.Normal lipoic acid group:rats lipoic acid do not do any treatment at40mg/kg intraperitoneal injection of15times.Electrical stimulation lipoic acid low-dosegroup: amygdala implanted electrodes,lipoic acid by intraperitoneal injection of20mg/kg after30min by120%seizure threshold thorns. Electrical stimulation of alpha lipoic acid and high dose group:amygdala lipoicacid by implanted electrodes after30min after intraperitoneal injectionof40mg/kg by120%seizure threshold stimulus once/day,a total of15times.Observed after electrical stimulation.Racine grading standards basedon observed behavior of animals in each group performance.24hours after administration,six rats in each group,perfusion brain was removed,wi th HE staining of rat hippocampal neuronal injury cases were detectedby immunohistochemistry Bcl-2,Bax and BDNF expression in hippocampal CA1region situation.Meanwhile Another six rats per group,decapitated,rapid separation of the hippocampus,the hippocampus was detected byWestern Blot method of Bcl-2,Bax and BDNF protein levels.Results:1Results of behavior:epileptic rats after repeated administration ofelectrical stimulation, seizures level gradually increased, eventually reachingmore than3times Ⅳ-Ⅴl evel attack. Electrical stimulation lipoic acidlow-dose group,the onset of electrical stimulation intensity lipoic acid andhigh dose group of rats compared to alleviate epilepsy group,mostlyconcentrated in Ⅱ-Ⅲgrade.Normal control group,sham operation group andnormal rats lipoic acid no seizures.2Results of HE staining：in normal control group, sham operationgroup and normal lipoic acid group:the hippocampus neurons arranged in neat rows,more levels,normal morphology,cytoplasmic transparent,uniform distribution of chromatin,nucleoli clear,no significant nerve cell loss.Epilepsy Group:hippocampal neurons arranged scattered,ill-defined,the gapincreases, significant neuronal loss,and showed eosinophilic neurons, manifested as cell shrinkage,chromatin condensation,nuclear condensation;electrical stimulation of low dose alpha lipoic acid group,electrical stimulation of high dose lipoic acid group:the hippocampus become normal cellmorphology,still neatly arranged,the number of surviving cells was significantly higher than the epilepsy group,only a small number of eosinophilic neurons.3Results of Western blot test：in Epilepsy Group rat hippocampal BDNFexpression levels compared with normal control group, sham operation groupand normal lipoic acid group was significantly higher (P<0.05), than theelectrical stimulation of low dose alpha lipoic acid group, electricalstimulation of high dose lipoic acid group was significantly lower (P<0.05);bax protein epilepsy group compared with the normal lipoic acid group, sham operation group, the normal control group, electrical stimulation of low-doselipoic acid group, electrical stimulation of high dose lipoic acid group wassignificantly higher (P<0.05). bcl-2expression in epilepsy group comparedwith the normal lipoic acid group, sham operation group, the control group,electrical stimulation of low-dose lipoic acid group, electrical stimulation ofhigh dose lipoic acid group was significantly lower (P<0.05).4Results of Immunohistochemical: Average optical density values ofBDNF in epileptic hippocampal CA1region compared with normal lipoic acidgroup, sham operation group, the control group was significantly higher (P<0.05); bax average optical density values compared with normal lipoic acidgroup, sham normal control group was significantly higher (P<0.05).Compared with the epilepsy group, in hippocampal CA1region of rats ofelectrical stimulation of low-dose lipoic acid group, electrical stimulation ofhigh dose lipoic acid group, the mean optical density value of BDNF,bcl-2was significantly higher (P<0.05),while bax average optical density valueswas significantly reduced.Conclusions:1In this study, chronic basolateral nucleus stimulation methodsuccessfully established model of chronic epilepsy electric ignition, α-lipoicacid effectively suppress epileptic seizures kindled rats, can reduce seizureslevel.2bcl-2epileptic to reduce the expression of anti-apoptotic proteins in thehippocampus, an increase of apoptosis protein bax expression. And to increasethe expression of BDNF.3α-lipoic acid can increase the expression of BDNF, bcl-2, reducedexpression of Bax, suggesting that α-lipoic acid by upregulating BDNF, bcl-2expression after epilepsy, reducing the expression of Bax, to prevent apoptoticpathway exert nerve protection. |
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