重组人红细胞生成素对癫痫持续状态大鼠海马p-Akt和XIAP的影响

史志勤; 王维平; 于江华; 郭力; 蒋国会; 王海祥; 范亚林

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重组人红细胞生成素对癫痫持续状态大鼠海马p-Akt和XIAP的影响

论著 | 更新时间：2026-01-09

- 重组人红细胞生成素对癫痫持续状态大鼠海马p-Akt和XIAP的影响
- Effects of rHuEPO on p-Akt and XIAP expressions in hippocampus of statural epilepticus rats
- 陆军军医大学学报 2009年31卷第15期页码：1453-1457
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  中图分类号： R338.26;R749.1;R977.1
- 纸质出版：2009
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史志勤,王维平,于江华,郭力,蒋国会,王海祥,范亚林.重组人红细胞生成素对癫痫持续状态大鼠海马p-Akt和XIAP的影响[J].陆军军医大学学报(原第三军医大学学报),2009,31(15):1453-1457.

　SHI Zhi-qin,WANG Wei-ping,YU Jiang-hua,GUO Li,JIANG Guo-hui,WANG Hai-xiang,FAN Ya-lin.Effects of rHuEPO on p-Akt and XIAP expressions in hippocampus of statural epilepticus rats[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(15):1453-1457.
史志勤,王维平,于江华,郭力,蒋国会,王海祥,范亚林.重组人红细胞生成素对癫痫持续状态大鼠海马p-Akt和XIAP的影响[J].陆军军医大学学报(原第三军医大学学报),2009,31(15):1453-1457. DOI：

　SHI Zhi-qin,WANG Wei-ping,YU Jiang-hua,GUO Li,JIANG Guo-hui,WANG Hai-xiang,FAN Ya-lin.Effects of rHuEPO on p-Akt and XIAP expressions in hippocampus of statural epilepticus rats[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(15):1453-1457. DOI：

摘要

目的观察重组人红细胞生成素(recombinant human EPO，rHuEPO)对戊四氮（Pentylenetetrazol

PTZ)点燃的癫痫持续状态(status epilepticus，SE)的SD大鼠海马神经元磷酸化蛋白激酶B(p-PKB/ p-Akt)和X-连锁凋亡抑制蛋白(X-linked inhibtor of apoptosis protein

XIAP)表达的影响

应用磷脂酰肌醇3激酶(phosphatidyl inositol 3 kinase， PI3K)抑制剂LY294002进一步探讨rHuEPO作用的可能机制。方法采用PTZ制作大鼠SE模型，将点燃后的大鼠随机分为PTZ组（PTZ+NS)、rHuEPO组（PTZ ＋rHuEPO）、LY294002组（PTZ＋LY294002＋rHuEPO）、LY294002溶剂二甲基亚砜 (DMSO)对照组（PTZ＋DMSO＋rHuEPO）

正常对照组腹腔注射生理盐水（n=35）。观察大鼠行为学和脑电图的改变; TUNEL法检测海马神经细胞的凋亡情况；免疫组织化学法观察p-Akt、XIAP的表达; RT-PCR法检测各组大鼠海马XIAP mRNA的表达; Western blot法检测各组大鼠海马Akt、p-Akt蛋白的表达。结果正常对照组仅见少量凋亡细胞，p-Akt和XIAP阳性细胞、p-Akt蛋白、XIAP mRNA均有少量表达；PTZ组与rHuEPO组、LY294002组、LY294002溶剂DMSO对照组比较，p-Akt和XIAP阳性细胞数、p-Akt蛋白表达及XIAP mRNA表达均减少（P0.05），凋亡细胞数增加（P0.05）；rHuEPO组、LY294002溶剂DMSO对照组与LY294002组比较，p-Akt和XIAP阳性细胞数、p-Akt蛋白表达及XIAP mRNA表达均增加（P0.05），凋亡细胞数减少（P0.05）。结论 rHuEPO在SE模型中活化了PI3K/Akt，提高p-Akt蛋白的表达

进而对线粒体凋亡途径的相关调控因子XIAP的表达进行了调控，从而介导线粒体凋亡途经

发挥抗凋亡、促存活的神经保护作用。

Abstract

Objective To observe the effects of recombinant human erythropoietin (rHuEPO) on the expressions of p-Akt and XIAP in hippocampus of statural epilepticus SD rats and the influence of LY294002

the inhibitor phosphatidyl inositol 3 kinase. Methods SD rats were divided into normal control group (normal saline

NS)

PTZ group (PTZ)

rHuEPO group (PTZ＋rHuEPO)

LY294002 group (PTZ＋LY294002＋rHuEPO)

DMSO control group (PTZ＋DMSO＋rHuEPO). Changes of behavior and EEG recordings were observed. The apoptotic neurons of the hippocampal region were detected by TUNEL method. The expressions of p-Akt and XIAP were detected by immunohistochemical method. The expression of XIAP mRNA located in the hippocampus was detected by RT-PCR. The expressions of Akt and p-Akt protein were determined by Western blot. Results A small quantity of apoptotic neurons and p-Akt and XIAP positive neurons but low expressions of protein p-Akt and XIAP mRNA were found in the normal control group. Decreased p-Akt and XIAP positive cells and the expressions of protein p-Akt and XIAP mRNA but increased apoptotic neurons were found in the PTZ group as compared with those in the rHuEPO group

LY294002 group and DMSO control group (P0.05). Increased p-Akt and XIAP positive cells and expressions of protein p-Akt and XIAP mRNA but decreased apoptotic neurons were found in rHuEPO group and DMSO control group as compared with those in the LY294002 group (P0.05). Conclusion rHuEPO could activate the signal delivery systems of PI3K/Akt in the SE model and increase the expression of p-Akt protein

and hence mediate the approach for chondriosome apoptosis and neuroprotective effect in anti-apoptosis and enhancement of neuron survival though the regulation of the expression of XIAP

the apoptosis related regulating factors.

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