气体信号分子硫化氢在热性惊厥脑损伤形成机制中的作用

Effect of hydrogen sulfide on brain damage induced by recurrent febrile seizures

目的:探讨硫化氢(H2S)对反复热性惊厥(febrile seizures,FS)脑损伤的影响。方法:大鼠随机分为对照组、FS组、FS+N aH S组、FS+H A(hydroxylam ine)组。采用热水浴诱导大鼠FS,隔日诱导1次,共10次。记录大鼠惊厥潜伏期、持续时间及强度;分光光度计法测定大鼠血浆中H2S含量;电镜观察海马神经元超微结构的改变;Tim m染色观察海马发芽情况;原位杂交和免疫组化分别观察c-fos基因和Fos蛋白表达情况。结果:FS+N aH S组和FS+H A组大鼠惊厥潜伏期、持续时间及强度的改变与FS组相比无明显差异;FS+N aH S组大鼠海马神经元超微结构损伤性改变较FS组明显减轻,而FS+H A组则明显加重;N aH S干预后海马苔藓纤维发芽减轻,而H A干预后海马发芽加重;N aH S的干预使c-fos基因和Fos蛋白表达降低,而H A的干预使其表达增强。结论:应用H2S外源性供体N aH S和胱硫醚-β-合成酶抑制剂H A的干预研究表明,气体信号分子硫化氢参与了热性惊厥脑损伤的发生与发展过程。

Objective To explore the effect of hydrogen sulfide （H2S） on brain damage induced by recurrent febrile seizures（FS）, Methods Rats were randomly divided into four groups： control group （37.0℃ water, n=16）, FS group（45.2℃ water, n=16）, FS＋NaHS group（45.2℃ water, n=16）, FS ＋ HA（hydroxylamine）group（45.2℃ water, n=16）. FS in rats were induced ten times by a bath of warm water, once every 2 days. The intensity, latency and duration of the seizure in rats were recorded. The plasma level of H2S was detected by a spectrophotometer. The ultrastruetural changes of hippoeampal neurons were observed under an election microscope. The development of mossy fiber sprouting（MFS） in hippoeampus was detected by Timm staining. The expression of c-fos gene and Fos protein were examined by in situ hybridization and immunohistoehemistry, Results There were no significant differences of seizure intensity, latency and duration among FS, FS ＋ Naris and FS ＋ HA groups. The electron microscope showed that the ultrastrueture of hippoeampal neurons changed after recurrent FS. The neuronal damage at the ultrastructure level was further aggravated in FS ＋ HA group, while the neuronal damage alleviated in FS ＋ Naris group. The evaluation of Timm-stained sections showed that MFS was evident in FS group, more notable in FS ＋ HA group while uneonspieuous in FS＋Naris group. The expression of c-los gene and Fos protein increased significantly after recurrent FS. Nails down regulated the expression of e-los gene and Fos protein, while HA enhanced the expression of them. Conclusion The study by using the exogenous donor of H2S and the inhibitor of eystathionine b-synthase （CBS） showed that H2S/CBS system might play an important role in the development of FS-induced brain damage.