褪黑素对海人酸致痫大鼠海马内TGF-β3水平的影响

EFFECTS OF MELATONIN ON TGF-β3 LEVEL IN HIPPOCAMPUS OF RATS WITH SEIZURES INDUCED BY KAINIC ACID

目的探讨褪黑素(me1atonin,MT)对海人酸(kainic acid,KA)致痫大鼠海马内TGF-β3的影响,进一步明确其在中枢内的作用。方法将实验大鼠随机分为3组:生理盐水对照组(NS组)、海人酸组(KA组)、褪黑素+海人酸组(MT+KA组)。各组大鼠给予相应试剂处理后观察并记录大鼠行为学改变,用免疫组织化学方法、RT-PCR检测大鼠海马内TGF-β3(transforming growth factor-β3)的表达情况及其mRNA变化。结果动物行为学观察显示,NS组无癫痫发作,KA组发作程度为Ⅲ-V级,MT+KA组为0-Ⅲ级;免疫组织化学结果显示,TGF-β3在3组大鼠海马内均有表达,其中KA组、MT+KA组较NS组表达增强,MT+KA组较KA组增强,差异具有显著性意义(P<0.05);RT-PCR结果显示,与NS组相比较,KA组、MT+KA组大鼠海马内TGF-β3 mRNA含量均升高;但MT+KA组升高较KA组多,差异具有显著性意义(P<0.05)。结论褪黑素能明显改善海人酸诱发的大鼠癫痫,增强海马内TGF-β3的表达,减轻海马神经元损伤,发挥中枢保护作用。

Objective To explore the effects of melatonin on the level of TGF-β3 in the hippocampus of rats with seizures induced by kainic acid.Methods The SD rats were randomly divided into 3 groups： NS（normal saline） group,KA（kainic acid） group,and MT＋KA（melatonin＋kainic acid） group.After treatment with relevant reagents,the behavior of rats was observed and recorded.The expression of TGF-β3 mRNA and protein in the rat hippocampus was examined by RT-PCR and immunohistochemistry respectively.Results The observation of rats＇ behavior showed that no seizure activity occured in the NS group,but III-V grade of seizure was seen in the KA group and 0-III grade in the MT＋KA group.Immunohistochemistry indicated that TGF-β3 was expressed in the hippocampus of all groups;the expression in the KA and MT＋KA groups was higher than that in the NS group;and it was is higher in the MT＋KA group than in the KA group.The differences between each group were significant（P〈0.05）.RT-PCR showed the same tendency of changes in the level of TGF-β3 mRNA as immunohistochemistry.Conclusion Melatonin can obviously improve the seizure induced by kainic acid,probably by enhancing TGF-β3 erpression in the hippocampus to prevent the hippocampal neurons from damage caused by epilepsy.