硝普钠控制性降压对兔脑神经元c-fos及细胞凋亡的影响

Effect of induced hypotension on brain neuronal c-fos and apoptosis in rabbits

目的通过观察硝普钠诱导的四种低血压水平对兔脑海马CA1区神经元超微结构、细胞凋亡及c-fos表达的影响,了解脑组织对低血压的耐受性以及探讨安全的降压低限。方法 30只新西兰兔随机均分为五组,MAP分别降至基础值的70%(Ⅰ组)、60%(Ⅱ组)、50%(Ⅲ组)、45%(Ⅳ组)和不降压(Ⅴ组)。目标血压维持1 h,复压2 h处死兔。透射电镜观察海马CA1区神经元超微结构,SP法测定该区c-fos表达,DNA末端标记技术(TUNEL)检测该区细胞凋亡。结果电镜下海马CA1区神经元:Ⅱ组出现细胞肿胀变化,Ⅲ、Ⅳ组出现核固缩及细胞凋亡。c-fos在所有控制性降压组表达增多(P<0.01)。Ⅱ、Ⅲ、Ⅳ组TUNEL荧光强度较Ⅰ、Ⅴ组增强(P<0.01)。结论硝普钠控制性降压可以使海马CA1区神经元出现部分凋亡改变,c-fos能对脑血氧供应变化作出快速反应,且其表达与神经元保护作用有关。

Objective To explore the brain＇s tolerance and the safe low limit to the hypotension through observing the effect of four different levels of sodium nitroprusside induced hypotension on neuronal ultrastructure and apoptosis and expression of c-fos in rabbits＇ hippocampal CA1 field. Methods Thirty New Zealand rabbits were equally randomized into five groups： mean arterial pressure fell to 70% （group Ⅰ ）, 60%（group Ⅱ ）, 50% （group Ⅱ ）and 45%（group Ⅳ） of the baseline and normal control group（group Ⅴ ）. After maintaining target blood pressure for 1 h, the rabbits were sacrificed 2 h after boosting pressure. The ultrastructure of CA1 field was observed with transmission electron microscopy. The expression of c-fos was assayed by immunohistochemical SP and apoptosis was detected by Tunel immunofluorescence in hippocampal CA1 neuron. Results In the transmission electron microscopy of hippocampal CA1 neuron, group Ⅱ appeared cellular swelling and groups Ⅲ and Ⅳ appeared karyopyknosis and apoptosis. The c-fos expression in CA1 neuron significantly increased in hypotension groups （P〈0. 01）. The TUNEL mean fluorescence intensity was much strengthen in groups Ⅱ, Ⅲ and Ⅳ than that in groups Ⅰ and Ⅴ （P 〈0. 01）. Conclusion Controlled hypotension with sodium nitroprusside can cause apoptosis in partial hippocampal CA1 neurons. C-fos can make rapid respond according to changes of brain blood and oxygen supply, and its expression may produce protective effects on neurons .