兰州大学机构库 >学院待认领
奥卡西平对戊四氮慢性致痫大鼠海马Bax、Bcl-2表达的影响
Alternative TitleEffect of Oxcarbazepine on Bax and Bcl-2 expression in hippocampus of epilepsy rats chronically kindled by pentylenetrazol
张洪源
Thesis Advisor王为民
2009-05-26
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword癫痫 奥卡西平 丙戊酸钠 戊四氮 Bax Bcl-2 细胞凋亡
Abstract目的:研究奥卡西平对戊四氮慢性致痫大鼠海马Bax, Bcl-2表达的影响,探讨其对海马神经元的保护作用。 方法:将80只成年Wistar大鼠随机分为8个组,正常对照组、模型组、丙戊酸钠阳性药物对照低剂量组(25 mg/ kg /d)、中剂量组(38 mg/ kg /d)、高剂量组(76 mg/ kg /d)、奥卡西平药物治疗低剂量组(165 mg/ kg /d)、中剂量组(250 mg/ kg /d)、高剂量组(500 mg/ kg /d )、每组10只。每天上午正常对照组给予等量的生理盐水(NS)腹腔注射,其余各组给予戊四氮(PTZ)(35 mg/ kg )腹腔注射,每日一次,直至达到点燃标准,(大约需要2周)。正常对照、模型组给与等量的NS,其余各组按上述剂量灌胃治疗3周。应用免疫组化染色法检测大鼠海马神经元Bax、Bcl-2蛋白的表达。 结果:1 .正常对照组无痫性发作,模型组有痫性发作,六组给药组均有痫性发作但发作级别降低。2 .与模型组比较,丙戊酸钠阳性药物对照组、奥卡西平药物治疗组癫痫发作的潜伏期延长(P<0.01),发作级别降低;奥卡西平低、中、高剂量组与丙戊酸钠低、中、高剂量组比较癫痫发作的潜伏期延长(P<0.01),发作级别降低。 3 . 大鼠海马神经元免疫组化染色Bax 、Bcl-2比较,正常对照组中Bax、Bcl-2蛋白染色阳性细胞低表达,与模型组比较,丙戊酸钠阳性药物对照组、奥卡西平药物治疗组Bcl-2蛋白染色阳性细胞增多,Bax蛋白染色阳性细胞减少。丙戊酸钠阳性药物对照组与奥卡西平药物治疗组比较,丙戊酸钠低剂量组、奥卡西平低剂量组之间无统计学意义(P>0.05);丙戊酸钠中剂量组、奥卡西平中剂量组之间有统计学意义(p<0.05);丙戊酸钠高剂量组、奥卡西平高剂量组之间有统计学意义(P<0.01);丙戊酸钠阳性药物对照低、中、高剂量组之间有统计学意义(P<0.01);奥卡西平药物治疗低、中、高剂量组之间有统计学意义(P<0.01)。4 . Bcl-2\Bax比值的比较,正常对照组、模型组之间无统计学意义(P>0.05);丙戊酸钠阳性药物对照组与奥卡西平药物治疗组比较,丙戊酸钠低剂量组、奥卡西平低剂量组之间无统计学意义(P>0.05);丙戊酸钠中、高剂量组、奥卡西平中、高剂量组之间有统计学意义(p<0.01);丙戊酸钠阳性药物对照低、中、高剂量组之间有统计学意义(P<0.01);奥卡西平药物治疗低、中、高剂量组之间有统计学意义(P<0.01)。 结论: 1 .丙戊酸钠、奥卡西平能使戊四氮致痫大鼠模型癫痫发作的潜伏期延长、发作的级别降低。2 . 奥卡西平低、中、高剂量对戊四氮致痫大鼠模型的癫痫发作的潜伏期延长、发作的级别降低优于丙戊酸钠低、中、高剂量。3 . 丙戊酸钠、奥卡西平对戊四氮致痫大鼠海马神经元有保护作用,能减轻癫痫发作后的海马神经元的凋亡,推测其机制可能与增强大鼠海马神经元Bcl-2的表达和降低Bax的表达有关。4 .Bcl-2\Bax 比值的改变与癫痫的神经元凋亡相关。5 . 奥卡西平中剂量和高剂量对海马神经元的保护优于丙戊酸钠中剂量和高剂量。6 . 丙戊酸钠对海马神经元的保护随剂量的增加而增强。7 . 奥卡西平对海马神经元的保护随剂量的增加而增强。
Other AbstractObjective :To studay the effects of the Oxcarbazepine on Bax and Bcl-2 expression of hippocampus in seizures rats induced by PTZ ,and to explore the protection of the different dosage of Oxcarbazepine for the neurons of the hippocampus。 Methodes :Eighty adult Wistar rats were randomlydivided into normalcontrol (NP)group,PTZ group、Valproate Sodium(VAP) durg positive Low dose group(25 mg/ kg /d )、medium dose group (38 mg/ kg /d) 、high dose group (76 mg/ kg /d),Oxcarbazepine(OXC) treatment Low dose group(165 mg/ kg /d),medium dose group(250 mg/ kg /d),high dose group(500 mg/ kg /d ),10 in each group . All the rats expcept those in NS group were intraperitoneal injection 35 mg/ kg of PTZ perday ,NP group were intraperitoneal injection the same times and dose of normal saline with the same method until the kindling criterion was reached (almost two weeks) . All the rats expcept those in NP group and PTZ group were intragastric administration dose of the above three weeks , NP group were and PTZ group were intragastric administration the same times and dose of NS with the same method ,The expression of Bax protein and Bcl-2 protein on the neurons of the hippocampus were analyzed by immunohistochemistry staining . Results : 1 : the normal control group had no seizure ,the epileptic group induced by PTZ had seizure , and the six mediaction administration groups had seizure too ,but the level of seizure were decreased . 2 : Compared with the PTZ gorup the lateneies of seizure were porlonged in the group of VAP durg positive group and OXC treatment group the difference had the significant meaning (p<0.01) , the level of seizure were decreased . OXC Low dose group medium dose group high dose group Compared with VPA Low dose group medium dose group high dose group the difference had the significant meaning (p<0.01) ,the level of seizure were decreased . 3 : the NP group the expression Bax protein and Bcl-2 protein were low . Compared with the PTZ group in the VAP durg positive group OXC treatment group the number of the positive neurons of Bcl-2 protein were increased , the number of the positive neurons of Bax protein were decreased . VPA Low dose group was indifferent statistically Compared with OXC Low dose group (p>0.05) ; medium dose group the difference had the meaning (p<0.05);high dose group the difference had the significant meaning (p<0.01 ) . VPA Low dose group medium dose group and high dose group the difference had the signific...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223834
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
张洪源. 奥卡西平对戊四氮慢性致痫大鼠海马Bax、Bcl-2表达的影响[D]. 兰州. 兰州大学,2009.
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