Ma Yu-Shan, Zhou Jun, Liu Hui, Du Yu, Lin Xue-Mei
Department of Anesthesia, West China Sencond Hospital, Sichuan University, Chendu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 May;44(3):397-401.
To investigate the effects of recombine human erythropoietin (rhEPO) on neural cells apoptosis and the expression of Caspase-3 protein in brain tissue of fetal rats after intrauterine hypoxic-ischemic brain injury.
Forty-four Sprague-Dawley rats on 19 days of pregnancy were divided into rhEPO treated group, ischemia-reperfusion group and sham-operated group. Intrauterine hypoxic-ischemic injury of fetal rats was induced by bilateral occlusion of the utero-ovarian artery for 20 min. rhEPO (5000 U/kg) was injected into rats through caudal vein in rhEPO treated group while saline was injected into rats in hypoxic-ischemic group 30 min before hypoxic-ischemic injury. The brain samples in rhEPO treated group and hypoxic-ischemic group were obtained at 30 min, 3 h, 6 h, 24 h and 48 h respectively after artery clamping. There was no hypoxic-ischemic injury in sham-operated group, so the brain samples were obtained at 24 hours after sham operation. Neuroapoptosis in brain tissue was measured by TdT mediated dUTP-biotin nick end labeling (Tunel) staining. The expression of Caspase-3 protein was observed by immunohistochemistry.
The number of apoptosis cells in fetal rat hippocampus after intrauterine hypoxic-ischemic increased progressively with reperfusion. Compared with the I/R group, the number of apoptosis cells decreased in rhEPO treated group (P < 0.01). The expression of Caspase-3 increased rapidly after 3 hours from the reperfusion in the I/R group. Compared with the I/R group, there was less expression of Caspase-3 in rhEPO treated group (P < 0.01).
rhEPO showed the effects to inhibit the apoptosis of fetal neural cells and the expression of Caspase-3 protein due to intrauterine hypoxic-ischemic brain injury.
探讨重组人促红细胞生成素(rhEPO)对宫内缺氧缺血性脑损伤胎鼠神经细胞凋亡及脑组织中半胱天冬酶-3(Caspase-3)蛋白表达的影响。
将44只孕19天的Sprague-Dawley大鼠分为rhEPO治疗组、缺血再灌注组和假手术组。通过双侧子宫卵巢动脉闭塞20分钟诱导胎鼠宫内缺氧缺血性损伤。rhEPO治疗组在缺氧缺血损伤前30分钟经尾静脉注射rhEPO(5000 U/kg),而缺氧缺血组注射生理盐水。rhEPO治疗组和缺氧缺血组分别在夹闭动脉后30分钟、3小时、6小时、24小时和48小时获取脑样本。假手术组无缺氧缺血损伤,在假手术后24小时获取脑样本。采用TdT介导的dUTP生物素缺口末端标记(Tunel)染色法检测脑组织中的神经细胞凋亡。通过免疫组织化学观察Caspase-3蛋白的表达。
宫内缺氧缺血后胎鼠海马区凋亡细胞数量随再灌注时间逐渐增加。与缺血再灌注组相比,rhEPO治疗组凋亡细胞数量减少(P < 0.01)。缺血再灌注组再灌注3小时后Caspase-3表达迅速增加。与缺血再灌注组相比,rhEPO治疗组Caspase-3表达较少(P < 0.01)。
rhEPO对宫内缺氧缺血性脑损伤导致的胎鼠神经细胞凋亡及Caspase-3蛋白表达具有抑制作用。