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目的探讨反复热性惊厥(FS)幼鼠在硫化氢(H2S)干预后其海马组织中IL-1β、IL-18水平的变化。方法 SD大鼠192只随机分为对照组、FS组、FS+硫氢化钠(NaHS)组、FS+羟胺(HA)组,每组各48只。采用热水浴诱导大鼠反复FS,每次诱导3~5 min,隔日诱导1次,共诱导10次。采用甲苯胺蓝染色了解各组幼鼠海马的病理变化;通过免疫组织化学法观察各组幼鼠IL-1β、IL-18蛋白表达变化;采用反转录聚合酶链反应方法检测各组幼鼠海马组织中IL-1β、IL-18 mRNA的表达情况。结果反复FS幼鼠海马组织中IL-1β和IL-18蛋白、IL-1βmRNA、IL-18 mRNA表达水平均增高,甲苯胺蓝染色显示其海马神经元排列紊乱,细胞核大小不一,部分细胞呈现空泡变性,部分浓缩凝固;NaSH干预后IL-1β蛋白、mRNA表达明显降低,FS+NaHS组IL-18蛋白、mRNA表达在1 d、3 d、7 d与FS组相比显著降低;HA干预6 h、3 d、7 d时IL-1β蛋白及mRNA表达均较FS组明显增高,6 h时IL-18的表达与FS组相比显著增高。结论 H2S对反复FS造成的脑损伤具有保护作用,其抑制IL-1β和IL-18的表达可能是其机制之一。
Objective To investigate the changes of IL-1β and IL-18 levels in hippocampus of repeated febrile seizures (FS) pups after hydrogen sulfide (H2S) intervention. Methods One hundred and ninety-two SD rats were randomly divided into control group, FS group, FS + sodium hydrosulfide (NaHS) group and FS + hydroxylamine group (HA). Induction of repeated FS in rats was carried out in a hot water bath. Each induction period was 3 to 5 minutes, followed by 1 induction every other day for 10 times. The histopathological changes of hippocampus in each group were observed by toluidine blue staining. The expression of IL-1β and IL-18 protein in the juveniles were observed by immunohistochemical method. The expression of IL-1β and IL-18 in juvenile rats was detected by reverse transcription polymerase chain reaction The expression of IL-1β, IL-18 mRNA in hippocampus of rats. Results The expression levels of IL-1β, IL-18, IL-1βmRNA and IL-18 mRNA in hippocampus of repeated FS rats were increased. Toluidine blue staining showed that the hippocampal neurons were disordered and the nuclei varied in size. The expression of IL-1βprotein and mRNA was significantly decreased after NaSH intervention. The expression of IL-18 protein and mRNA in FS + NaHS group was significantly lower than that in FS group on1d, 3d, 7d The expression of IL-1βprotein and mRNA at 6 h, 3 d and 7 d after intervention was significantly higher than that of FS group, and the expression of IL-18 at 6 h was significantly higher than that of FS group. Conclusions H2S may have a protective effect on brain injury induced by repeated FS. One of the mechanisms may be its inhibition of the expression of IL-1β and IL-18.