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新生鼠HIE后海马CA1区NMDAR表达和细胞凋亡及促红细胞生成素作用

Effect of rhEPO on N-methy-D-aspartate receptor expression and neurons apoptosis in hippocampal CA1 in neonatal rat model of cerebral hypoxic-ischemia
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摘要 【目的】研究新生大鼠缺氧缺血性脑损伤(hypoxic-ishemic brain damage,HIBD)后海马CAI区N-甲基-D-天门冬氨酸受体(NMDAR)表达和神经细胞凋亡及重组人红细胞生成素(rhEPO)对其的影响。【方法】建立缺氧缺血脑损伤新生鼠模型及重组人红细胞生成素治疗模型。用SP免疫组化及原位切口末端标记(TUNEL)的方法检测缺氧缺血(HI)后rhEPO干预后不同时间点NMDA受体I型亚单位(NR1)阳性细胞表达及神经细胞凋亡的情况。【结果】①NR1蛋白在HIBD后2 h表达增强,6 h达高峰(F=189.772,P<0.01),然后逐渐下降,24 h表达明显低于假手术组(F=325.601,P<0.01),72 h开始恢复。rhEPO治疗组与HIBD组相比CA1区的NR1蛋白表达在6 h降低(t=-9.188,P<0.01),而24 h以后的NR1蛋白的表达却有所增加(t=2.522,P<0.05)。②HIBD后6 h右侧海马CA1区出现凋亡细胞,24 h显著增高,48 h达高峰后逐渐下降,但72 h仍高于假手术对照组(F=71.587,P<0.01)。rhEPO治疗组与HIBD组相比CA1区的凋亡细胞数在各时间点均明显减少,尤其在24 h最明显(t=-9.251,P<0.01)。【结论】外源性rhE-PO可通过多种途径对HIBD后的脑组织起到保护作用。 [Objectives] To study the expression of N-methy-D-aspartate receptor(NMDAR) and neurons apoptosis in hippocampal CA1 and the Recombinant Human Erythropoietin(rhEPO) on the expression after hypoxic-ischemic brain damage(HIBD) in neonatal rats, [Methods] An animal model of neonatal hypoxic-ischemic brain damage and therapeutic effect of the rhEPO on HIBD intraperitoneally were set up. The expression of NR1 positive cells was detected with immunohistochemistry and neurons apoptosis was observed with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining. [Results] ①The NRlexpression increased sharply at 2 h and reached the peak at 6 h after HIBD(F= 189,772,P〈0. 01 ), then decreased gradually and showed an expression lower than control group at 24 h(F=325. 601 ,P〈0. 01). The expression began to rise at 72 h. The rhEPO could largely reduce the NRlexpression in 6 h after HIBD(t=-9. 188,P〈0. 01)and increase the expression after 24 h(t= 2. 522,P〈0.05),②Apoptosis of neurons in CA1 region was observed at 6 h after HIBD and increased obviously at 24 h and then decreased at 72 h, which was still higher than that in so control group (F= 71. 587,P〈0.01). In the intervention group, the number of apoptotie neurons was much fewer than that in HIBD group, especially in 24 h(t=-9. 251 ,P〈0.01). [Conclusion] It suggested that intraperitoneal administration with rhEPO had cerebral protective effects on HIBD through several paths.
出处 《中国儿童保健杂志》 CAS 2006年第2期163-165,共3页 Chinese Journal of Child Health Care
基金 陕西省自然科学研究基金项目[2004K14-G3(2)]
关键词 重组人红细胞生成素 N-甲基-D-天门冬氨酸 凋亡 脑缺氧 脑缺血 新生大鼠 recombinant human erythropoietin N-methy-D-aspartate receptor apoptosis cerebral hypoxic cerebral ischemia neonatal rats
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