低分子肝素抗新生大鼠大脑皮层神经细胞缺氧性凋亡  

Effect of low molecular weight heparin on hypoxia-induced apoptosis in primary cultured neonate rat cerebral cortical neurons

作　　者：文珠[1] 李扣华[2] 唐宁 胡国柱[4] 张进[4] 聂荣庆[4] 

机构地区：[1]江西省医学科学研究所,江西南昌330006 [2]泰州市人民医院神经内科,江苏泰州220000 [3]深圳市西丽人民医院,广东深圳518055 [4]江西省中医药研究院,江西南昌330077

出　　处：《中国病理生理杂志》2007年第2期370-372,共3页Chinese Journal of Pathophysiology

摘　　要：目的:探讨低分子肝素对体外培养的新生大鼠大脑皮层神经细胞缺氧性凋亡的作用机制。方法:应用“neurobasal加B27 supplement”体外培养大鼠大脑皮层神经细胞,并在缺氧条件下使用Hoechst 33342荧光染色法、免疫细胞化学染色法观察低分子肝素对原代神经细胞的抗凋亡作用。结果:在250-500 U/L的浓度范围內,低分子肝素能降低缺氧诱导的神经细胞凋亡率(P<0.05),并且较BDNF(50μg/L)抗凋亡阳性对照组的凋亡率更低(P<0.05)。低分子肝素(500 U/L)增加缺氧的神经细胞Bcl-2蛋白的表达(P<0.05),减少Bax蛋白的表达(P<0.01),提高Bcl-2/Bax比值(P<0.01)。低分子肝素500 U/L组的Bcl-2/Bax比值比正常对照组、BDNF抗凋亡阳性对照组和凋亡阳性组都高(P<0.05)。结论:低分子肝素通过上调缺氧神经细胞Bcl-2表达和下调Bax表达,提高Bcl-2/Bax比值减少缺氧的神经细胞凋亡。AIM： To investigate the mechanism by which low molecular weight heparin （LMWH） inhibits apoptosis of primary cultured cerebral cortical neurons caused by hypoxia. METHODS： The anti - apoptosis effect of LMWH on primary cultured neurons was observed by methods of the primary culture of cerebral neurons of postnatal rats in free - serum with neurobasal medium supplied with 2% B27 supplement, hypoxic culture of neurons, Hoechst 33342 staining and immunocytochemistry. RESULTS： At concentrations of 250 -500 U/L, LMWH reduced apoptosis rate of cerebral cortical neurons induced by hypoxia （P 〈 0. 05 ） and apoptosis rate was lower in LMWH groups than that in BDNF （50 μg/L） group （P 〈0. 05）. LMWH （500 U/L） increased Bcl- 2 protein expression （P 〈 0. 05） and decreased Bax protein expression （P 〈 0. 01 ） in the cerebral cortical neurons induced by hypoxia, the ratio of Bcl -2/Bax was improved （P 〈 0. 01 ）. The ratio of Bcl -2/Bax in LMWH （500 U/L） group was higher than that in normal control group, BDNF group and apoptosis positive group （P 〈 0. 05 ）. CONCLUSION ： LMWH at concentrations of 250 - 500 U/L is able to prevent cerebral cortical neurons from apoptosis in primary culture under hypoxia. The effect of anti - apoptosis may be related to up - regulation of Bcl -2 protein expression, down -regulation of Bax -2 protein expression, and increase in the ratio of Bcl -2/Bax.

关 键 词：肝素 低分子量 神经原 缺氧 细胞凋亡 大鼠 

分 类 号：R363[医药卫生—病理学]