慢性脑缺血大鼠脑组织线粒体蛋白质组与能量代谢相关性研究  

Brain mitochondria proteome and energy metabolism in rats after chronic cerebral hypoperfusion

作　　者：贺晓丽[1] 毕明刚[1] 杜冠华[2] 

机构地区：[1]中国医学科学院药用植物研究所药理毒理研究中心,北京100193 [2]中国医学科学院药物研究所国家药物筛选中心,北京100050

出　　处：《中国药理学通报》2012年第9期1200-1205,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金重点项目(No 30630073)

摘　　要：目的探讨慢性脑缺血大鼠脑组织线粒体蛋白质组与能量代谢相关性,以期揭示慢性脑缺血疾病的线粒体机制。方法通过差速离心分离大鼠脑线粒体,检测脑线粒体能量代谢相关的氧化磷酸化指标,应用凝胶电泳技术构建大鼠脑线粒体蛋白质组表达图谱;通过结扎大鼠双侧颈总动脉建立大鼠慢性脑缺血模型,分析比较慢性脑缺血时脑线粒体蛋白质表达谱的改变,从脑线粒体蛋白质组角度阐述慢性脑缺血与能量代谢的关系。结果实验发现,与正常对照组相比,慢性脑缺血大鼠脑线粒体ADP/O及氧化磷酸化效率明显降低,蛋白质组结果显示慢性脑缺血大鼠NADH脱氢酶复合体亚基、细胞色素C氧化酶亚基、丙酮酸脱氢酶(硫辛酰胺)β、乙酰辅酶A乙酰转移酶、烯醇化酶、醛缩酶C等表达量降低,而3-含氧酸辅酶A转移酶、4-氨基丁酸转氨酶等表达量增加。结论实验表明,慢性脑缺血大鼠能量代谢功能及能量代谢相关酶发生了很大变化,慢性脑缺血疾病机制与线粒体具有密切关系。Aim To study the relationship between brain mitochondria proteome and energy metabolism in rats after chronic cerebral hypoperfusion. Methods Rats models of cognitive deficits were established with permanent bilateral common carotid arteries occlusion （2VO）. Cerebral cortex mitochondria was isolated to study the oxidative phosphorylation function. 2D electrophoresis was used to explore the difference of brain mitochondria proteome. MALDI-TOF MS was used toprovide sensitive mass spectral data for 16 unique proteins that changed in abundance between sham and 2VO rats. Results Parameters of oxidative phosphorylation in 2VO rats changed, the ADP/O rate and OPR were significantly decreased in rat brains after 2VO. In these proteins, the expression of NADH dehy- drogenase （ubiquinone） 1 alpha subcomplex 5, cyto- chrome c oxidase, subunit Via, pyruvate dehydrogen- ase （lipoamide） beta, Acetyl-CoA acetyhransferase,enolase 2, aldolase C decreased, while 3-oxoacid CoA transferase 1 and 4-aminobutyrate aminotransferase increased in 2VO rats. Conclusion These findings indicate that the change of energy metabolism itself and the enzymes related to energy metabolism in 2VO rats isinvolved in the chronic cerebral hypoperfusion in the clinic.

关 键 词：慢性脑缺血 线粒体 蛋白质组 双侧颈总动脉结扎 能量代谢 大鼠 

分 类 号：R332[医药卫生—人体生理学] R322.81[医药卫生—基础医学]