低氧刺激诱导体外培养的大鼠脑皮质星形胶质细胞内neuregulin-1表达上调

A SIGNIFICANT UP-REGULATION OF THE NEUREGULIN-1 IN THE CULTURED RAT CORTICAL ASTROCYTES INDUCED BY HYPOXIA

Neuregulin-1(NRG-1)是神经胶质及神经元产生的细胞间信号转导蛋白。该蛋白通过与ErbB受体结合,对神经系统的正常发育、成熟发挥重要作用,也在缺血性脑损伤时起神经保护作用。为探讨体外培养的星形胶质细胞受缺氧刺激后NRG-1的表达特点,本实验利用体外培养的大鼠脑皮质星形胶质细胞,采用免疫组织化学和Westernblot方法,比较了正常培养和低氧复氧条件下星形胶质细胞中NRG1的表达。结果显示:正常培养的星形胶质细胞中有NRG-1的表达,但含量不高;低氧复氧培养后星形胶质细胞NRG1的表达量随着复氧时间的延长缓慢增加,至复氧8h,其表达量陡然升高,达到峰值后又逐渐降低,甚至降至正常水平以下。本研究表明,在低氧缺血性脑损伤后,星形胶质细胞反应性大量产生NRG1的时间相对滞后。由此提示,低氧缺血性脑损伤后,立即使用外源性神经保护剂为宜。

Neuregulin-1 （ NRG-1） is a signaling protein among cells produced by glial cells and neurons. It plays a critical role via ErbB receptors not only in maturation and development of the nervous system, but also in neural protection in ischemic brain damage. To investigate the changes of the expression of NRG-1 in the cultured astrocytes after conditioned hypoxia,we cultured the rat cortical astrecytes and examined the expression of NRG-1 in both normal and hypoxia conditions by means of fluorescent immunecytechemical labeling and semiquantitative Western blot. Results showed that normal cultured astrocytes expressed a relative lower level of NRG-1. The expression of NRG-1 slowly increased after hypoxia/reoxygenation, and dramatically increased to reach the highest level at 8 h after reoxygenation, then decreased again. The results suggest that the astrecytes could not express enough NRG-1 immediately after hypoxia and ischemia; therefore, administration of neuroprotectants would be necessary as early as possible after hypoxia and ischemic brain damage.