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Research Of The Effects Of Glu And GABA Capacity In Brain And The Expression Of Multidrug Resistance Gene Of Pingxian Powder On Chronic Epileptic Rats

Posted on:2011-01-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:L Z PanFull Text:PDF
GTID:1114360308472403Subject:Chinese Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Objective:To study the effects of Pingxian Powder to Glu and GABA capacity and the expression of multidrug resistance gene in the hippocampi in brain tissue of epileptic the young big rat to explore the possible antiepileptic mechanism of Pingxian Powder.Experiment oneMethods:In SPF level experiment, adopted sixty Wistar young big rats of 28d old, weighting 70±10g, half-and-half sexes; which were divided into six groups at random according to the number random list,10 in every group, normal control group (Group A), model control group (Group B), high,middling,low dose of Pingxian Powder (Group C,D,E), western medicine control group (Group F), PTZ of subconvulsions dose was injected into abdomen of every rat except for Group A to reproduce epileptic kindling model, After reproduce epileptic model successfully,0.9% NS was given to Group A and Group B, Pingxian Powder was given to Group C, Group D and Group E and Phenobarbital was given to Group F; After treating 21d, rats were killed and taken brain tissue, Glu and GABA capacity in brain tissue were examined by biochemistry method and biochemistry technology.Results:Glu capacity in brain tissue of Group B was creased apparently contrasting to Group A; however, Glu capacity in brain tissue of Group C,D,E was decreased to varying degrees contrasting to Group B (P<0.01) (P<0.05). GABA capacity in brain tissue of Group B was decreased apparently contrasting to Group A; but which was creased to varying degrees in Group C,D,E contrasting to Group B (P <0.01) (P<0.05)Conclusions:Pingxian Powder may promote threshold of epileptic seizures and reduce the excitability of cerebral cortices by inhibiting the activities of excitatory amino acid of experimental epileptic big rat and promote the activities of inhibitory amino acid, to rebalance excitatory amino acid and inhibitory amino acid, efficiently inhibiting epileptic seizures.Experiment twoMethods:in this study,In the base of building the animal model of refractory epilepsy by pilocarpine, we investigated p-gp/MDR1 mRNA and MRP1 mRNA influence by different medicine intervention. According to functional parmeter and pathohistology to analyses curative effect. Then the expression and distribution of P-gp/MDR1mRNA and MRP 1 mRNA was research, Localization in brain of rats with medically intractable epilepsy. We intended to study the role of p-gp/MDR1 mRNA and MRP1 mRNA on the drug resistance mechanisms of medically intractable emilepsy,and investigate the effect on them by the herbs of PingXian PowderExperimental animal and group:alike experiment one. the expression of P-gp and mRNA of MDR1 and MRP1 was investigated in cortex and hippocampus of rats by the herbs of PingXian powder.we observed the expression and distribution of P-gp/MDR1 mRNA and MRP1 mRNA in cortex and hippocampus of rats by Realtime PCR,immunohistochemical method and Western blotting. We intented to study the role of P-gp/MDR1 mRNA and MRP1 mRNA on the drug resistance mechanisms of medically intractable epilepsy,and investigate the effect on the them by the herbsof PingXian powder.Results:(1)Compared with that of the nomal control group,P-gp/MDR1 mRNA and MRP1 mRNA expression in cortex and hippocampus on rats with intractable epilepsy of the blank model group,high,middling,low dose of Pingxian Powder showed an obviously statistical increasing(P<0.05); The amount of P-gp/MDR1 mRNA and MRP1 mRNA expression from low to high was by middling dose of Pingxian Powder, high dose of Pingxian Powder, low dose of Pingxian Powder, the blank model group,the western medicine group.(2) there was no obviously statistical difference between cortex and hippocampus about P-gp/MDR1 mRNA and MRP1 mRNA expression in model control group, high,middling,low dose of Pingxian Powder and western medicine group.(P>0.05)Conclusions:1 The expression of P-gp/MDRl mRNA and MRP1 mRNA are significantly increased in cortex and hippocampus of rats with medically intractable epilepsy. They are concerned with drug resistance of medically intactable epilepsy.2 The present study indicated that seizure may induce over-expression of P-gp/MDR1 mRNA and MRP1 mRNA in cortex and hippocampus of rats with medically intractable epilepsy,seizure and AED may be involved in up-regulation of P-gp/MDR1 mRNA and MRP1 mRNA expression.3The herbs of Pingxian Powder may inhibit multidrug transporters, can decrease over-expression of P-gp/MDR1 mRNA and MRP1 mRNA. The mechanism on the herbs of Pingxian Powder healing refractory epilepsy may be it's inhibiting multidrug transporters.
Keywords/Search Tags:Pingxian Powder, Epilepsy, Glu, GABA, P-glycoprotein, multidrug resistance gene
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