高迁移率族蛋白B1对癫痫大鼠海马P-糖蛋白表达的影响
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Effect of high-mobility group box-1 on P-glycoprotein expression in the hippocampus of epileptic rats
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    摘要:

    目的:探讨高迁移率族蛋白B1(high-mobility group box-1,HMGB1)对癫痫大鼠脑P-糖蛋白(P-glycoprotein,P-gp)表达的调控作用-方法:将60只雄性SD大鼠随机分为假手术组,癫痫组,低-中-高剂量HMGB1干预组,每组12只-采用海马微量注射海人酸(kainic acid,KA)制作癫痫大鼠模型,各HMGB1干预组于注射KA前15 min,通过侧脑室微量注射不同剂量重组HMGB1蛋白进行干预-记录癫痫大鼠自注射KA后至初次达到Ⅲ级发作的时间(seizure onset time,SOT),作为评价癫痫发作易感性指标;造模成功24 h后处死大鼠,分别采用免疫组化法-实时定量荧光PCR和蛋白质免疫印迹法检测并比较各组大鼠海马组织损伤-P-gp多药耐药基因1(multidrug resistance-1,mdr1)mRNA及蛋白表达-结果:与癫痫组比较,中-高剂量HMGB1干预组SOT缩短(P < 0.05),海马组织结构紊乱,海马CA3区神经元过度丢失(P < 0.05),海马mdr1 mRNA及P-gp表达增加(P < 0.05)-而低剂量HMGB1干预组与癫痫组比较,以上各项指标差异则无统计学意义(P > 0.05)-结论:HMGB1可增加癫痫鼠发作易感性,加重海马组织损伤,促进海马组织P-gp过表达-

    Abstract:

    Objective:To investigate the regulation of high-mobility group box-1(HMGB1)on P-glycoprotein(P-gp)expression in the hippocampus of epileptic rats. Methods:Sixty male SD rats were randomly divided into the sham operation group,epilepsy group,low,medium and high doses of HMGB1 pretreated groups with 12 rats in each group. Various doses of recombinant HMGB1 protein were injected intraventricularly 15 min before micro-injection of kainic acid(KA)into the hippocampus. The latency period to the onset of stage Ⅲ first seizure time was observed to assess epileptic susceptibility and all the rats were sacrificed after 24 hours of the operation. The damage of the hippocampal tissue,the expression levels of mdr1 mRNA and P-gp were detected by immunohistochemical method,real-time PCR and Western blot,respectively. Results:Compared with the epilepsy group,the SOT of epileptic seizure latency in the medium and high doses of HMGB1 pretreated groups were lower than that of the epilepsy group(P < 0.05),the damage of the hippocampal tissue and neuron loss in the hippocampus CA3 area were increased(P < 0.05),and the expression levels of mdr1 mRNA and P-gp were up-regulated in the medium and high doses of HMGB1 pretreated groups(P < 0.05),but there was no significant differences between the low-doses HMGB1 pretreated group and epilepsy group(P > 0.05). Conclusion:HMGB1 could increase seizure susceptibility,the damage of hippocampal tissue and the over-expression levels of P-gp in the hippocampus of seizure rats.

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黄贤径,郝劲博,狄 晴,余 年,张燕芳,闻 芳,陈 艳.高迁移率族蛋白B1对癫痫大鼠海马P-糖蛋白表达的影响[J].南京医科大学学报(自然科学版),2014,(8):1029-1033

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  • 收稿日期:2014-03-26
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  • 在线发布日期: 2014-08-03
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