地塞米松对海人酸致（癇）大鼠脑P-糖蛋白表达的影响

目的：探讨地塞米松对海人酸致痫大鼠脑P-糖蛋白（P-gp）表达的影响.方法：将SD大鼠随机分为假手术组（Sham组,n=8）、癫痫组（EP组,n=12）、地塞米松干预癫痫组（DEX组,n=12）.后两组采用海马注射海人酸方法制作癫痫模型,DEX组癫痫造模前30 min给予腹腔注射地塞米松0.4 mg/kg.分别记录各组大鼠达到Ⅲ级和Ⅴ级发作时所需的时间（潜伏期）,初次至第6次≥Ⅳ级发作的间隔时间作为评价癫痫发作严重程度的指标;大鼠术后24 h处死,使用HE染色和免疫组织化学方法,比较各组海马CA3区、齿状回、杏仁核复合体区P-gp表达及脑损伤情况.结果：①Sham 组未见癫痫发作;DEX组与EP组达到Ⅲ级发作的潜伏期分别为（87.92±45.80）min和（67.50±22.91）min,达到Ⅴ级发作的潜伏期分别为（103.33±51.27 ）min和（75.60±22.10）min,差异均无统计学意义（P〉0.05）;与EP组相比,DEX组样发作严重程度降低（P=0.004）;②与EP组相比,DEX组于所观察的脑区损伤均减轻,以海马CA3区和杏仁核复合体区较为显著;③与Sham组比较,EP组各观察脑区P-gp表达均明显升高（P〈0.01）;与EP组相比,DEX组海马CA3区和杏仁核复合体区P-gp表达显著减少（P〈0.05）,而在齿状回表达量差异无统计学意义（P=0.078）.结论：地塞米松可降低海人酸致痫大鼠发作严重程度和脑损伤,抑制P-gp表达上调,其中以海马CA3区和杏仁核区较为显著.

The effect of dexamethasone on P-glycoprotein expression in the brain of kainic acid-induced seizure rats

Objective：To investigate the effect of dexamethasone on P-glycoprotein （P-gp） expres sion in rats with brain kainic acid（KA） epilepsy. Methods.. SD rats were randomly divided into the shamoperated group （Sham group,n 8）,the epilepsy group （EP group,n=12）,and the epilepsy rats intervened with dexamethasone （DEX group,n=12）. The epilepsy rats veceived KA injection and the rats of DEX group received intraperitoneal injection of dexamethasone（0.4 mg/kg）30 min prior to KA. The latency to Grade Ⅲ and Ⅴ onset of each group were recorded as well as the frequency of severe seizures. All rats were killed 24 h after KA treatment. HE staining and immunohistochemical methods were used to compare the differences of P-gp expression in the hippoeampal CA3 area, dentate gyrus,and amygdala complex area and brain damage. Results： （1）No seizures were observed in Sham group. The latency to Grade Ⅲ onset in DEX and EP groups were （87.92 ± 45.80）min and （67. 50 ± 22. 91）min, and to Grade V onset were （103.33 ± 51. 27）min and （75.60± 22.10）minrespectively. There was no statistical difference （P〉0.05）. Compared with EP group, the severity of epileptic seizures of DEX group decreased （P=0. 004）. （2）Compared with EP group, the damage of epileptic related brain areas in DEX group was reduced. （3）A small amount of P-gp was expressed in the brains of Sham group. The P-gp expression of EP group was significantly enhanced （P〈0.01）. Compared with the EP group, P-gp expression in hippocampus CA3 area and the arnygdala complex of DEX group was significantly reduced （P〈0.05）, but there was not significant difference in dentate gyrus （P〈0. 078）. Conclusion： Dexamethason ecan reduce seizure severity and brain damage of epileptic rats and block up regulation of P-gp in the rat brain.