中药复方熄风胶囊对难治性癫痫大鼠多药耐药基因MDR1mRNA表达的影响
|
摘要
目的探讨中药复方熄风胶囊对氯化锂—匹罗卡品致难治性癫痫模型大鼠脑组织MDR1mRNA表达的影响。方法建立氯化锂—匹罗卡品癫痫大鼠模型。实验大鼠随机分为8组:正常对照组(空白组)、模型对照组(模型组)、熄风胶囊低剂量组(熄低组)、熄风胶囊中剂量组(熄中组)、熄风胶囊高剂量组(熄高组)、卡马西平治疗组(CBZ组)、熄风胶囊中剂量+卡马西平组(熄卡组)、熄风胶囊中剂量+1/2卡马西平组(熄卡低组)。熄低、中、高组分别予熄风胶囊0.33 g、0.66 g、0.99 g,浓缩剂2 m L;CBZ组予CBZ 20 mg/kg;熄卡、熄卡低组分别予熄风胶囊0.66 g和CBZ20 mg/kg、CBZ 10 mg/kg;模型组和空白组分别予生理盐水2 m L。每天上午灌胃一次,共持续60天。给药结束后检测各组大鼠脑组织MDR1mRNA的表达。结果与空白组比较,其余各组的MDR1mRNA的基因表达均上调(P<0.05);与模型组比较,熄中组、熄卡低组、熄卡组和CBZ组的MDR1mRNA表达均下降(P<0.05);与CBZ组相比,熄卡低组和熄卡组的基因表达均明显降低(P<0.05)。结论熄中组、熄卡低组、熄卡组、CBZ组对MDR1mRNA表达有抑制作用,且熄卡低组和熄卡组对MDR1mRNA表达的抑制作用比单用卡马西平作用更明显。
Objective To study the effect of Chinese herbal compound Xifeng capsule on different expression of MDR1 mRNA in the brain tissue of epileptic rats induced by lithium chloride-pilocar. Methods Epileptic rat model was established by lithium chloride-pilocarpine. Rats were randomly divided into eight groups: normal control group,model control group,Xifeng capsule low-dose treatment group( Xifeng low-dose group),Xifeng capsule middle-dose treatment group( Xifeng middle-dose group),Xifeng capsule high-dose treatment group( Xifeng high-dose group),carbamazepine treatment group( CBZ group),Xifeng middle-dose + carbamazepine treatment group( xi-car group),Xifeng capsule middle-dose + 1/2dose carbamazepine treatment( xi-car low group). Xifeng low,medium and high group was respectively given 0. 33 g,0. 66 g and 0. 99 g,thickening agent 2 m L; CBZ dose group was given CBZ 20 mg/kg; Xi-car and Xicar low group was respectively given Xifeng capsule 0. 66 g thickening agentr 2m L and CBZ 20mg/kg,CBZ10mg/kg; normal control group and model control group was respectively given 2 m L saline solution. The rats were intragastric administration once a day in the morning for 60 days. The MDR1 mRNA expression ofeach group was detected. Result Real-time RT-PCR results showed that: comparing with normal control group,the expression of MDR1 mRNA in the rest groups were up-regulation. Comparing with model group,the expression of MDR1 mRNA of the CBZ group,Xifeng middle-dosegroup,Xifeng middle-dose + CBZ groupand Xifeng middle-dose + 1/2 CBZ group was declined( P < 0. 05). Comparing with CBZ group,the expression of MDR1 mRNA of Xifeng middle-dose + CBZ groupand Xifeng middle-dose + 1/2 CBZ group was declined( P < 0. 05). Conclusion The CBZ group,Xifeng middle-dosegroup,Xifeng middle-dose + CBZ group and Xifeng middle-dose + 1/2 CBZ group had inhibitory effect on the expression of MDR1 mRNA,and Xifeng middle-dose group,the inhibitory effect of Xifeng middle-dose + 1/2 CBZ group is more obvious than CBZ group.
Objective To study the effect of Chinese herbal compound Xifeng capsule on different expression of MDR1 mRNA in the brain tissue of epileptic rats induced by lithium chloride-pilocar. Methods Epileptic rat model was established by lithium chloride-pilocarpine. Rats were randomly divided into eight groups: normal control group,model control group,Xifeng capsule low-dose treatment group( Xifeng low-dose group),Xifeng capsule middle-dose treatment group( Xifeng middle-dose group),Xifeng capsule high-dose treatment group( Xifeng high-dose group),carbamazepine treatment group( CBZ group),Xifeng middle-dose + carbamazepine treatment group( xi-car group),Xifeng capsule middle-dose + 1/2dose carbamazepine treatment( xi-car low group). Xifeng low,medium and high group was respectively given 0. 33 g,0. 66 g and 0. 99 g,thickening agent 2 m L; CBZ dose group was given CBZ 20 mg/kg; Xi-car and Xicar low group was respectively given Xifeng capsule 0. 66 g thickening agentr 2m L and CBZ 20mg/kg,CBZ10mg/kg; normal control group and model control group was respectively given 2 m L saline solution. The rats were intragastric administration once a day in the morning for 60 days. The MDR1 mRNA expression ofeach group was detected. Result Real-time RT-PCR results showed that: comparing with normal control group,the expression of MDR1 mRNA in the rest groups were up-regulation. Comparing with model group,the expression of MDR1 mRNA of the CBZ group,Xifeng middle-dosegroup,Xifeng middle-dose + CBZ groupand Xifeng middle-dose + 1/2 CBZ group was declined( P < 0. 05). Comparing with CBZ group,the expression of MDR1 mRNA of Xifeng middle-dose + CBZ groupand Xifeng middle-dose + 1/2 CBZ group was declined( P < 0. 05). Conclusion The CBZ group,Xifeng middle-dosegroup,Xifeng middle-dose + CBZ group and Xifeng middle-dose + 1/2 CBZ group had inhibitory effect on the expression of MDR1 mRNA,and Xifeng middle-dose group,the inhibitory effect of Xifeng middle-dose + 1/2 CBZ group is more obvious than CBZ group.
引文
[1]Honchar MP,Olney JW,Sherman WR.Systemic cholinergic a-gents induce seizures and brain damage in lithium-treated rats.[J].Science,1983,220(4594):323-325.
[2]余倩.小剂量反复注射匹罗卡品建立颞叶癫痫大鼠模型的研究[J].贵州医药,2012,36(2):162-163.
[3]Racine RJ.Modification of seizure activity by electrical stimulation.Ⅱ.Motor Seizure,Electroencephalogr[J].Clin Neurophysiol,1972,32:281-294.
[4]Seegers U,Potschka H,L9scher W.Expression of the multidrug transporter P-glycoprotein in brain capillary endothelial cells and brain parenchyma of amygdala-kindled rats[J].Epilepsia,2002,43(7):675-684.
[5]Kubota H,Ishihara H,Langmann T,et al.Distribution and functional activity of P-glycopro tein and multidrug resistance-associated proteins in human brain microvascularend othelial cells in hippocampal sclerosis[J].Epilepsy Res,2006,68(3):213-228.
[6]Sisodiya S.Drug resistance in epilepsy:not futile,but complex?[J].Lancet Neurology,2003,2(6):331.
[7]Marroni M,Marchi N,Cucullo L,et al.Vascular and parenchymal mechanisms in multiple drug resistance:a lesson from human epilepsy[J].Current Drug Targets,2003,4(4):297-304.
[8]Lee G,Schlichter L,Bendayan M,et al.Functional expression of P-glycoprotein in rat brain microglia[J].J Phaimacol Exp Ther,2001,299(1):204-212.
[9]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9):229-232.
[10]刘新红,余年,狄晴,等.小檗碱对癫痫大鼠脑组织P糖蛋白表达的影响[J].临床神经病学杂志,2013,26(3):191-194.
[11]王三明,赵烨,康乐,等.雷公藤内酯对癫痫大鼠P-糖蛋白表达影响[J].辽宁中医药大学学报,2014,16(4):21-23.
[12]晏玉奎,邱彩霞,刘泉坤,等.虎杖苷调节海人酸致痫鼠颞叶、海马区P-糖蛋白表达的实验研究[J].中华中医药学刊,2014,32(5):1164-1166.
[13]刘金民,郑香春.中药柴贝止痫汤对难治性癫痫大鼠多药耐药基因MDR1表达的研究[J].天津中医药.2009,26(6):472-475.
[2]余倩.小剂量反复注射匹罗卡品建立颞叶癫痫大鼠模型的研究[J].贵州医药,2012,36(2):162-163.
[3]Racine RJ.Modification of seizure activity by electrical stimulation.Ⅱ.Motor Seizure,Electroencephalogr[J].Clin Neurophysiol,1972,32:281-294.
[4]Seegers U,Potschka H,L9scher W.Expression of the multidrug transporter P-glycoprotein in brain capillary endothelial cells and brain parenchyma of amygdala-kindled rats[J].Epilepsia,2002,43(7):675-684.
[5]Kubota H,Ishihara H,Langmann T,et al.Distribution and functional activity of P-glycopro tein and multidrug resistance-associated proteins in human brain microvascularend othelial cells in hippocampal sclerosis[J].Epilepsy Res,2006,68(3):213-228.
[6]Sisodiya S.Drug resistance in epilepsy:not futile,but complex?[J].Lancet Neurology,2003,2(6):331.
[7]Marroni M,Marchi N,Cucullo L,et al.Vascular and parenchymal mechanisms in multiple drug resistance:a lesson from human epilepsy[J].Current Drug Targets,2003,4(4):297-304.
[8]Lee G,Schlichter L,Bendayan M,et al.Functional expression of P-glycoprotein in rat brain microglia[J].J Phaimacol Exp Ther,2001,299(1):204-212.
[9]谢炜,陈伟军,孟春想,等.柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P糖蛋白表达的影响[J].中国实验方剂学杂志,2013,19(9):229-232.
[10]刘新红,余年,狄晴,等.小檗碱对癫痫大鼠脑组织P糖蛋白表达的影响[J].临床神经病学杂志,2013,26(3):191-194.
[11]王三明,赵烨,康乐,等.雷公藤内酯对癫痫大鼠P-糖蛋白表达影响[J].辽宁中医药大学学报,2014,16(4):21-23.
[12]晏玉奎,邱彩霞,刘泉坤,等.虎杖苷调节海人酸致痫鼠颞叶、海马区P-糖蛋白表达的实验研究[J].中华中医药学刊,2014,32(5):1164-1166.
[13]刘金民,郑香春.中药柴贝止痫汤对难治性癫痫大鼠多药耐药基因MDR1表达的研究[J].天津中医药.2009,26(6):472-475.