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Alpha-DHEC神经保护作用依赖核因子Kappa B的激活

NEUROPROTECTIVE EFFECT OF ALPHA-DIHYDROERGOCRYPTINE DEPENDS ON ACTIVATION OF NUCLEAR FACTOR KAPPA B

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【作者】 郑淑秋李彤禤亦雄林穗珍陈丽君颜光美

【Author】 ZHENG Shu qiu, LI Tong, XUAN Yi xiong, LIN Sui zhen, CHEN Li juen, YAN Guang mei (Department of Pharmacology, Sun Yat Sen University of Medical Science, Guangzhou 510080, China)

【机构】 中山医科大学药理教研室!广东广州510089

【摘要】 目的 探讨α 二氢麦角隐亭 (alpha DHEC)的神经保护作用与核因子KappaB(NF κB)激活的相关性。 方法 采用大鼠大脑中动脉闭塞诱导神经元凋亡 ,用迁移率改变法 (EMSA)检测NF κB活性 ,流式细胞仪 (FCM )和TUNEL法检测神经元凋亡。结果 脑缺血 1,3,6和 12h均伴有NF κB激活 ,其中以缺血 3h尤为显著。 10 0 μg·kg-1和 15 0 μg·kg-1的alpha DHEC预防给药均可明显抑制缺血 3h诱发的神经元凋亡 ,当用PDTC选择性阻断NF κB活性后 ,alpha DHEC的神经保护作用明显减弱。结论 alpha DHEC的神经保护作用可能依赖NF κB的激活。

【Abstract】 AIM To investigate the relationship between the neuroprotective effect of alpha dihydroergocryptine (alpha DHEC) and the activation of nuclear factor Kappa B (NF Kappa B). METHODS Adult male rats were subjected to cerebral ischemia induced by middle cerebral artery occlusion (MCAO). DNA binding activity of NF Kappa B was determined with electrophoretic mobility shift assay (EMSA) in animals subjected to varying durations of cerebral ischemia. Neuroapoptosis induced by ischemic damage was measured by deoxynucleotidy transferase mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM) analysis. RESULTS No change was observed in nuclear NF Kappa B DNA binding in normal animal. A low level of constitutive NF Kappa B DNA binding was detected in animals subjected to cerebral ischemia of 1 h, and significant increse in the amount of active NF Kappa B in nuclear extracts was observed after cerebral ischemia of 3 h, 6 h, and 12 h. Peak of NF Kappa B DNA binding was observed at the time point of 3 h. Animals subjected to cerebral ischemia of 3 h potentially initiates neuroapoptosis and activates NF Kappa B in nuclear extract. Alpha DHEC (100 μg·kg -1 and 150 μg·kg -1 ) showed significant protective effect on neuroapoptosis induced by cerebral ischemia of 3 h, and inhibiting NF Kappa B activation using 100 mg·kg -1 pyrrolidinedithiocarbamate (PDTC) in the continuous presence of alpha DHEC, the neuroprotective effect of alpha DHEC was blocked. CONCLUSION The findings suggest that the neuroprotetive effect of alpha DHEC may depend on the activation of NF Kappa B.

【基金】 国家杰出青年基金!( 3 962 5 0 2 2 );广东省博士启动基金资助项目!( 110 0 )
  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2000年12期
  • 【被引频次】2
  • 【下载频次】59
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