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Study On Mechanism Of The Gastrodiae Capsule And Gastrodin Combined Carbamazepine To Penicillin-kindled Rats

Posted on:2015-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:X J DangFull Text:PDF
GTID:2254330431951204Subject:Pharmacy
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AimStudy the gastrodia capsule and its active ingredients gastrodine combined carbamazepine for epilepsy inhibition in rats induced by penicillin. The gastrodia capsule and its active ingredient combine carbamazepine in vivo pharmacokinetic interactions in epileptic rats. To study the gastrodia capsule and its active ingredient gastrodine joint carbamazepine hippocampus P-gp expression in epilepsy rat by immunohistochemical and Western blot. To study the gastrodia capsule and its active ingredient gastrodine joint carbamazepine for epilepsy rat hippocampus P-gp expression n in the hippocampus of the epilepsy rats by real-time fluorescent quantitative PCR.Methods1the SD rats were divided into6groups(each group of6):blank control group, carb amazepine group, carbamazepine combined the gastrodia capsule group, carbamazepine com bined gastrodine group and the gastrodia capsule group. Blank control group were received the normal saline. The other group were given the corresponding drugs, once a day for s even days. At60min after the oral dose, each rat received PG (760U-kg-1i.p.) at sevent h day. The level of attack, duration, incubation time were recorded each animal according to the scale described above.2The kindled rats were randomly divided into six groups.90SD rats were randomly divided into five groups (18per group):CBZ group, CBZ and the gastrodia capsule group, the gastrodia capsule group, CBZ and gastrodine group, gastrodin group, and kindled control group. Blank control group were received the normal saline. The other group were given the corresponding drugs, once a day.6rats were selected randomly from each group at first day.6rats were selected randomly from each group at seventh day. The last rats were selected at fifteenth day.The blood and brain tissue were taken at the stipulated time, the blood drug concentration and drug concentration were analyzed after processed. Pharmacokinetic data in each group was calculated by the pharmacokinetic software DAS2.0.3The kindled rats were randomly divided into six groups.108SD rats were randomly divided into six groups (18per group):CBZ group, CBZ and the gastrodia capsule group, the gastrodia capsule group, CBZ and gastrodine group, gastrodin group, and kindled con trol group. Blank control group were received the normal saline. The other group were gi ven the corresponding drugs, once a day.6rats were selected randomly from each group at first day.6rats were selected randomly from each group at seventh day. The last rats were selected at fifteenth day.The hippocampus was immediately removed and weighed fro m brain. The hippocampus was stored at-20℃which was used for General Pathology, I mmune histochemical method, Western blot and RT-PCR.Results1, The level of attack, duration, incubation time had significantly affect between carbamazepine and other groups. The study found that gastrodia capsule joint group is better than combined the active gastrodia group.At the same time, the gastrodia capsule group and the active gastrodia group were less of the inhibition effect than carbamazepine group.2, The vivo pharmacokinetic data of carbamazepine were rinfluenced by the gastrodia capsule and the active gastrodia.carbamazepine. The vivo pharmacokinetic data of gastrodia were also rinfluenced by carbamazepine. The max blood concentration of drug and cerebral concentrationo of carbamazepine is on the decline with the increase days.This trend improve after joining the active gastrodia, while single gastrodine for carbamazepine has no effect.3, P-glycoprotein expression in hippocampus of rats was increased accompanily with days of given drugs in the carbamazepine group.The expression of P-glycoprotein were declined CBZ and the gastrodia capsule group than in the carbamazepine group. The study found that the gastrodia capsule can repair damaged cells, but carbamazepine and the active gastrodia has no effect by general pathology.4, P-glycoprotein expression in hippocampus of rats was increased more in kindled rats than cantrol group.P-glycoprotein expression in hippocampus of rats was increased accompanily with days of given drugs in every groups. But the gastrodine were increased P-gp expression weaker than carbamazepine.5, MDRla gene expression were increased was increased accompanily with days of given drugs in every groups MDRlb gene were declined at the seventh day,while increased again at the fifteenth day. MDRla and MDRlb gene were morpholin knockdown by the gastrodia capsule, on the contrary the active gastrodia were morpholin knockup. Abcc gene expression were raised Carbamazepine group were most obvious, for Abccl gene has inhibition, gastrodia elata, gastrodia elata, by contrast, will increase the expression of MRP1/Abccl gene.ConclusionThe gastrodia capsule and its active gastrodine joint carbamazepine has significant inhibitory effect for epileptic rats induced by penicillin.Its inhibitory effect is better than carbamazepine group. The vivo pharmacokinetic data of carbamazepine were rinfluenced by the gastrodia capsule and the active gastrodia.carbamazepine. The vivo pharmacokinetic data of gastrodia were also rinfluenced by carbamazepine. The gastrodia capsule can repair the damaged cells. The gastrodia capsule would also affect the expression of P-GP in the hippocampus, MDR1and MRP1/Abccl gene. The study provided new thought and new theory for study of anti-epileptic drugs.
Keywords/Search Tags:carbamazepine, rhizoma gastrodiae, penicillin, epilepsy model, P-GP, pharmacokinetic, Western blot, real-time fluorescent quantitative PCR, immunehistochemical method
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