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重组人红细胞生成素通过抑制GAPDH核内过表达减少脑缺血大鼠神经元凋亡

关艳中, 郭冉, 念红, 金秀东^*

牡丹江医学院基础医学院生理学教研室；黑龙江省高校生物学重点学科实验室，牡丹江 157011

摘要

本文旨在探讨重组人红细胞生成素(recombinant human erythropoietin, rhEPO)是否通过抑制甘油醛三磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase, GAPDH)核内过表达减少脑缺血再灌注大鼠神经元凋亡。大脑中动脉栓塞法制作脑缺血再灌注大鼠模型。48只Sprague-Dawley大鼠随机分为假手术组、生理盐水对照组和EPO处理组。TTC染色、尼氏染色及Hoechst-33258免疫荧光分别观察EPO对脑组织缺血和缺血半影区神经元凋亡的影响；Hoechst-33258和GAPDH免疫荧光双染观察EPO对GAPDH核内过表达的影响。结果显示，与生理盐水对照组相比，再灌注同时开始给予rhEPO (3 000 U/kg，3次/日，腹腔注射)显著抑制缺血再灌注引起的神经元GAPDH核内过表达，同时显著减少半影区神经元凋亡数目，减轻缺血性脑损伤。以上结果提示，rhEPO可能通过抑制GAPDH核内过表达减少脑缺血再灌注大鼠半影区神经元凋亡，为探讨EPO的神经保护机制提供了实验证据。

关键词： 促红细胞生成素; GAPDH; 脑缺血; 神经元凋亡

分类号：R338

[Involvement of inhibition of nucleus GAPDH over-expression in erythropoietin's reduction of neuronal apoptosis induced by brain ischemia/reperfusion in rats.] [Article in Chinese]

GUAN Yan-Zhong, GUO Ran, NIAN Hong, JIN Xiu-Dong^*

Department of Physiology, Basic Medical College； Laboratory of Key Disciplines in Universities of Heilongjiang Province—Biology, Mudanjiang Medical University, Mudanjiang 157011, China

Abstract

To study whether recombinant human erythropoietin (rhEPO) reduces neuronal apoptosis through inhibiting over-expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in nucleus induced by brain ischemia/reperfusion in rats, 48 adult Sprague-Dawley rats were randomly divided into 3 groups: sham, saline and EPO groups. Animal models of brain ischemia/reperfusion were established by middle cerebral artery occlusion in rats. The effects of EPO on the sizes of ischemia tissue were observed by TTC staining. The over-expression of GAPDH in nucleus was detected by Hoechst-33258 and anti-GAPDH antibody double staining. The neuronal apoptosis in penumbral was detected by Nissl's staining and Hoechst-33258 immunofluorescence, respectively. The results showed that rhEPO treatment (3 000 U/kg, three times daily, i.p.) apparently reduced the sizes of infarct brain tissue in ischemia/reperfusion rats. rhEPO inhibited over-expression of GAPDH in nucleus of apoptotic neurons. In the meantime rhEPO decreased the number of apoptotic neurons in ischemia/reperfusion rats. These results suggest that rhEPO may induced reduction of neuronal apoptosis in penumbra may be through inhibiting over-expression of GAPDH in nucleus of apoptotic neurons induced by ischemia/reperfusion. Reduction of GAPDH over-expression in nucleus may play a pivotal role in EPO inhibiting neuronal apoptosis in cerebral ischemia/reperfusion rats, providing experimental evidence for EPO neuro-protecting effects against ischemia/reperfusion.

Key words: GAPDH; erythropoietin; cerebral ischemia; neuronal apoptosis

收稿日期：2011-11-04　　录用日期：2012-01-16

通讯作者：金秀东　　E-mail: md-guan@163.com

引用本文：

关艳中, 郭冉, 念红, 金秀东. 重组人红细胞生成素通过抑制GAPDH核内过表达减少脑缺血大鼠神经元凋亡[J]. 生理学报 2012; 64 (3): 269-274.

GUAN Yan-Zhong, GUO Ran, NIAN Hong, JIN Xiu-Dong. [Involvement of inhibition of nucleus GAPDH over-expression in erythropoietin's reduction of neuronal apoptosis induced by brain ischemia/reperfusion in rats.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (3): 269-274 (in Chinese with English abstract).