小檗碱对Aβ_(25-35)诱导大鼠PC12细胞损伤的保护作用  

Protective effects of berberine on Aβ_(25-35) induced cytotoxicity in rat pheochromocytoma cells

作　　者：李彩莲[1] 王芳[1] 刘超[1] 林凡凯[1] 金悠[1] 龙利红[1] 陈建国[1] 

机构地区：[1]华中科技大学同济医学院药理学系,武汉430030

出　　处：《中国科技论文》2006年第4期269-275,共7页China Sciencepaper

基　　金：国家杰出青年科学基金(30425024);教育部优秀青年教师资助计划(2003)

摘　　要：目的:探索小檗碱对β-淀粉样蛋白25-35(Aβ_(25-35))诱导肾上腺嗜铬细胞瘤(PC12)细胞损伤的作用。方法:采用25μM Aβ_(25-35)处理 PC12细胞36 h 建立细胞损伤模型,应用细胞增殖抑制实验(MTT)评价细胞存活率,并检测细胞谷胱甘肽过氧化物酶(GSH-P_X)和超氧化物歧化酶(SOD)的活性、细胞内活性氧(ROS)和胞内游离钙浓度([Ca^(2+)]_i)的变化以及细胞凋亡。结果:给予 Aβ_(25-35)后,胞内 GSH-P_X 和 SOD 活性降低,细胞内 ROS 含量和[Ca^(2+)]_i 增加,并表现出凋亡的形态和特征,与凋亡相关的 caspase-3蛋白表达明显升高。小檗碱(0.01-10μM)预处理24小时,再给予25μMAβ_(25-35)后,细胞存活率增加、GSH-P_X、SOD 活性升高、细胞内 ROS 含量降低、[Ca^(2+)]_i 降低、凋亡细胞数减少和 caspase-3蛋白表达明显下降。结论:小檗碱对 Aβ_(25-35)诱导的 PC12细胞损伤具有明显保护作用,其机理可能与其抗氧化、拮抗[Ca^(2+)]_i 和抑制细胞凋亡有关。Objective To explore the protective effects of berberine on Aβ_(25-35)induced cytotoxicity in rat pheochromocytoma cells.Methods PC12 cells treated with 25 μM Aβ_(25-35)for 36 h underwent cell death as determined by MTT evaluation.The present study is also conducted by measuring the antioxidant enzyme activities. The apoptotic death has been tested by DAPI nuclei staining.The generation of reactive oxygen species(ROS), intracellular calcium concentration and caspase-3 activity have been examined.Results Pretreatment with berberine 0.01-10 μM for 24 h prior to Aβ_(25-35)exposure significantly elevated the cell survival and antioxidant enzyme activities.Preincubation with berberine also significantly prevented the cells from Aβ_(25-35)induced apoptosis, ROS generation and elevation of intracellular calcium concentration.Conclusion These results suggest that berberine has protective effect on Aβ_(25-35)-induced PC12 cell death,and its effect may be through antioxidative property and decreased expression of caspase-3 in a dose-dependent manner.

关 键 词：小檗碱 PC12细胞 Aβ_25-35 活性氧 caspase-3 

分 类 号：R749.16[医药卫生—神经病学与精神病学]