一氧化碳和一氧化氮对热性惊厥大鼠海马神经元凋亡的影响

Effect of carbon monoxide and nitric oxide on the apoptosis of hippocampal neurons in rats with febrile seizures

摘要:

目的：热性惊厥(FS)是小儿时期最常见的惊厥性疾病,反复FS可造成海马神经元的损伤,同时血红素氧合酶(HO)/一氧化碳(CO)系统和一氧化氮合酶(NOS)/一氧化氮(NO)系统明显上调并相互影响。该研究使用HO的抑制剂锌原卟啉Ⅸ(ZnPP-Ⅸ)和NOS的抑制剂Nω硝基-L-精氨酸甲酯(L-NAME)对FS时两个系统进行干预,探讨此两个系统对反复FS大鼠海马神经元凋亡的影响。方法：采用热水浴诱导大鼠FS,隔日诱导1次,共诱导10次。21日龄SD大鼠随机分为4组对照组,FS组,FS+ZnPP-Ⅸ组,FS+L-NAME组。TUNEL法对各组大鼠海马CA1区神经元进行凋亡检测。结果：FS组大鼠海马CA1区凋亡细胞数较对照组多225%,两组比较,差异有显著性(P<0.01),FS+ZnPP-Ⅸ组大鼠海马CA1区凋亡细胞数较FS组和对照组分别多62%和425%(均P<0.01),FS+L-NAME组大鼠海马CA1区凋亡细胞数较FS组低38%(P<0.01),较对照组多100%(P<0.05)。结论：反复FS时,外源性给予HO抑制剂ZnPP-Ⅸ可导致海马神经元的凋亡增多,而NOS的抑制剂L-NAME可致海马神经元的凋亡减少,提示HO/CO系统可保护FS神经元的损伤,NOS/NO系统可加重FS神经元的损伤。

Abstract:

OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/ carbon monoxide (HO/CO) system and nitric oxide sythase/ nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm water bath (45.2 ℃), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 ℃ water bath exposure), FS, FS + ZnPP-Ⅸ (HO inhibitor) and FS+ L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P<0.01). The apoptotic cells in the FS+ZnPP-Ⅸ group increased by 62% and 425% compared with those in the FS and the Control groups (both P <0.01). The apoptotic cells in the FS+L-NAME group decreased by 38% compared with those in the FS group (P<0.01) and increased by 100% compared with those in the Control group ( P<0.05 ). CONCLUSIONS: onclusions In recurrent FS, exogenous administration of HO inhibitor ZnPP-Ⅸ may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.