The Research Of Nimodipine's Protection Effect Towards Rats' Hippocampi From Penicillin-induced Seizures

Background These years scholars found that the Ca²⁺ and calcium channel have played a important role in Epilepsy's occurrence, development and prognosis along with the progression of mechanism of epileptic seizure. It provided a new way to protect brain tissue when epilepsy attacks and to exploitate the new medicine of anti-epileptic.Ca²⁺ exists extensivly in cells and extracellular fluid of human body. It not only participate the nerve conduction, transmitter emission articulo progression, but also participate cell differentiation, proliferation, regeneration et al. As a important second messenger associate various kinds of enzyme reaction system and function protein. Because of the complex function of neuron, the culmination sophisticated lattice structure between each cell to construct the organism association. The normal ratio of Ca²⁺ of intra-cell to extra-cell is 1/20000. This ratio is a dynamic balance formed by various kinds of cellular organ, electrical difference and calcium channel. The balance is the basis to execute the normal function of cells. If the balance was breaked, the malfunction of cells' will happen, cellular organ will be damage, even the cell will die.The paroxysmal depolarization shift formed by transient and quick inflow and slow inflow of Ca²⁺ was considered to be the basis of epileptic discharge. The ambulation of Ca²⁺ was completed by calcium channel. And the anti-epileptic mechanism of some anti-epileptic medicine concerned with calcium channel, such as Ethosuximide depress absence seizure by prevention the calcium channel inthalamic neuron. Though the structure of gabapentin was samed to GABA, it didn't effect the GABA receptor derectly. It's affinity site was calcium channel.Calcium channel was divided to two kinds, voltage-dependent calcium channel() and receptor-operated calcium channel (ROCC ). On the basis of voltaic formed by Ca2+, the VDCC was devided to F-, L-, N-, P-, Q-, R-. Among them the L- type channel mainly resides in neuron memb and cytodendrite. It may generate persistence voltage and be sensitiveness to Nimodipine. Scholars of China had applied Nimodipin to djunctive therapy epilepsy in clinical in 1995.Heat shock protein(HSP) was a culmination conservative protein created by some organism or cell when it was stimulated by stress. HSP may protect cells from stress, so it was named stress protein. It was a indicatrix to verifier the extent of cell's damage.Objective To investigate the influence of nimodipine on expression of heat shock protein 70, neuron apoptosis and ultramicrostructure in hippocampi of rats' epilepsy model induced by penicillin, to proof the protection of nimodipine to rats' brain in epileptic attack.Methods Wistar rats was used in this experiment. The criterion is two months old, Weight 150¹80g. Provided by Shantou university medicine college. Epilepsy model established by injection penicillin into abdominal cavity.Divided into three group, penicillin group, nimodipine intervention group and blank comparison group. Infuse nimodipine into rats' stomach 30 minutes before the injection of penicillin. After the injection of penicillin 24 hours break the rats' skull and get the brain, then investigate the expression of heat shock protein 70 in hippocampi ofrats by immunochemistry methods. Investigate the neuron apoptosis by TUNEL. Observation the ultramicrostructure in hippocampi by TEM. Result Nimodipine intervention group's seizure degree is lighter than the penicillin group and occurred later, some of rats of this group didn't take place seizure. The result of immunochemistry methods accord with the naked eyes, nimodipine intervention group's expression of heat shock protein(HSP) is less than single penicillin group, x2=4.625, P=0.031, P<0.05. And there is no expression of HSP in blank comparison group. TUNEL stain show that the apoptosis cell decreased manifest in nimodipine intervention group. TEM observed only the chondrosome and rough endoplasmic reticulum broadened lightly in nimodipine intervention group. But the ultramicrostructure was damaged obviously in penicillin group.Conclusion Bihydrogen pyridine Calcium channel blocking agent nimodipine could resist the seizure of rats induced by penicillin on a certain extent. And nimodipine could restrain the expression of heat shock protein 70 in hippocampi of rats' epilepsy model. Nimodipine may decrease the neuron apoptosis in hippocamp and may lessen the damage of neuron when epileptic attack.