The Expression Of Bim And Caspase-3in Hippocampus Of Status Epilepticus Rats

Objective：Epilepsy is a common disease of the nervous system, its high incidenceand high morbidity not only leads to a serious economic burden to patients and its families,but also often cause psychological problems. Status epilepticus is a clinical emergency andsevere, if not timely manner terminate its attack, can cause irreversible brain damage,hippocampus is the particularly vulnerable region. Epilepsy is not a medical problem but asocial problem, and therefore the mechanisms and treatment of epilepsy and SE of thestudy never stop. Recent studies have found that seizures associated with neuronalapoptosis. The BH3-only protein Bim is a proapoptotic member of the Bcl-2family areexpressed in many organizations, involved in a variety of diseases processes. Caspasefamily is a protease system directly induce the disintegration of the cell apoptosis, andCaspase-3is located in the core link of cascade. Currently the activation of caspase-3isconsidered to be a sign of neuronal apoptosis.This study aims to throughpilocarpine-induced SE rat model as the research object, to investigate the relationshipbetween the expression of Bim and Caspase-3in hippocampus of rats with SE andneuronal apoptosis.Methods：1.The60adult male Sprague-Dawley (SD) rats were randomly dividedinto control group (n=8) and epilepsy group (n=52).2.Atropine Sulfate was given to reduce the peripheral effects of cholinergic beforeintraperitoneal injection of pilocarpine-induced SE model, based on whether the epilepticseizures level group will be divided into SE groups and non-SE group.SE group after1hof status epilepticus terminated with chloral hydrate,the control group with saline insteadof pilocarpine,and the rest deal with epileptic group. 3.Rats were observed behavioral performance, harvested materials after24h, the leftcerebral hemisphere to HE staining, tunel staining and immunohistochemical staining(Caspase-3),detected the damage、 apoptosis of hippocampus CA1area neurons andCaspase-3positive cells staining. The right hemisphere of the hippocampal tissues wasperformed blot method (western blotting),in order to detect the changes of Bim expressionin hippocampus (26kd).Comprehensive analysis therelationships between themorphological changes of hippocampal neurons and Bim, Caspase-3expression.Result：1. In the rat model induced SE by pilocarpine, there are12did not reach attacklevel (non-SE group) in the epileptic group(52rats), successfully induced SE are40(76.9%success rates),12are deaths of this40rats(30%mortality within24h), controlgroup and the non-SE rats are no death.2. Compared with the control group and the non-SE group, the number of neurons inthe hippocampal CA1region of rats with HE staining of SE group was significantlyreduced (SE group:55.75±5.48,control group:102.50±3.74,non-SE group:100.04±2.73;P<0.05);but the Tunel staining positive cells was significantly increased(SE group:5.40±1.46, control group:0.82±0.36, non-SE group：3.24±0.71; P<0.05);western blottingdetection of Bim protein increased significantly, the ratio of the average optical density (SEgroup:0.58±0.36, control group:0.19±0.20, non-SE group:0.22±0.17; P<0.01);Caspase-3immunohistochemical staining positive cells increased significantly(SE group:21.32±1.74, control group:2.47±1.31, non-SE groups:2.23±2.08; P<0.05). Correlation analysisshowed that there is a positive correlation relationship (r=0.901, P<0.001) between Bimand Caspase-3’s overexpression in SE group rats hippocampal; between Bim’soverexpression and Tunel positive staining also have a positive correlation relationship(r=0.844，p<0.01).Conclusion： Application of pilocarpine-induced SE model has a high success rateand low mortality.24h after SE rats hippocampal neuronal necrosis and apoptosis. Theexpression of Bim and Caspase-3in hippocampus of rats24h after SE increased, whilehippocampal neurons appear necrosis and apoptosis. Statistical analysis showed that there is a positive correlation between Bim and Caspase-3’s overexpression; between Bim’soverexpression and Tunel positive staining neurons also have a positive correlationrelationship, suggesting that Bim may be involved in the pathophysiology process ofhippocampal neuronal damage after SE and play an important role.