皮质发育障碍模型大鼠海马区阳离子-氯离子转运体基因表达变化的研究  

Changes of expression of cation-chloride cotransporter genes in hippocampus of cortical dysplasia:experiment with rat

作　　者：龙莉莉[1] 肖波[1] 宋延民[1] 王康[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008

出　　处：《中华医学杂志》2007年第19期1351-1354,共4页National Medical Journal of China

基　　金：教育部高等学校优秀青年教师教学科研奖励计划基金资助项目(2001-182);高等学校博士学科点专项科研基金(2003-172)

摘　　要：目的探讨阳离子-氯离子转运体 NKCC1(内向 Na^+,K^+-2Cl^-协同运输)、KCC2(外向K^+-Cl^-协同运输)mRNA 在皮质发育障碍致痫机制中的作用。方法在 SD 大鼠孕17 d 腹腔内注入卡莫司汀(BCNU)制作皮质发育障碍模型;Nissl 染色观察 P60 d 仔鼠病理变化;P60 d 用逆转录-聚合酶链反应(RT-PCR)方法检测两组雄性仔鼠海马区 NKCC1、KCC2 mRNA 的表达。结果 Nissl 染色湿示海马区域异位细胞异常聚集。实验组海马区 NKCC 1mRNA 表达明显上调(NKCC1/肌动蛋白的比值,实验组0.70±0.13、对照组0.48±0.09,P<0.01),KCC2 mRNA 表达明显下调(KCC2/肌动蛋白的比值,实验组0.54±0.10、对照组0.81±0.15,P<0.01)。结论 NKCCl mRNA 上调和 KCC2mRNA 下调的共同作用可能与皮质发育障碍致痫密切相关。Objective To investigate the roles of cation-chloride cotransporters-Na, K, 2Cl^- cotransporter-1 （ NKCC1 ） and K^＋-Cl^- cotransporter-2 （ KCC2 ） in the epileptogenesis of cortical dysplasia. Methods Six pregnant SD rats were given intraperitoneal injection of 1-3-bis-chloroethyl-nitrosourea （BCNU） on the embryonic day 17 （E17） and gave birth of 56 pups （experimental group） on the day P21. Five pregnant SD rats were given intraperitoneal injection of normal saline and gavr birth of 48 pups （control group） on the day E21. Sixty days after birth the brains of 24 male pups in the experimental group and 22 male pups in the control group selected randomly were taken out to isolate the hippocampus. Cresylviolet staining was applied to observe the histological alterations in the hippocampus, RT-PCR was used to detect the mRNA expression of NKCC1 and KCC2. Results Cresyl-violet staining revealed heterotopic cell clusters within the hippocampus, RT-PCR showed that the ratio of NKCC1 to β-actin of the experimental group was 0. 70±0. 13, significantly higher thant that of the control group （0. 48±0. 09, P 〈0. 01 ） ; while the ratio of KCC2 to β-actin of the experimental group was 0. 54±0. 10, signigficantly lower than that of the control group （ 0. 80 ± 0. 15, P 〈 0. 01 ） . Conclusion The upregulation of NKCC1 mRNA and the concomitant downregulation of KCC2 mRNA may be deeply related to the mechanism of epileptogenicity in cortical dysplasias.

关 键 词：发育障碍 海马 Γ-氨基丁酸 阳离子-氯离子转运体 

分 类 号：R742[医药卫生—神经病学与精神病学]