北五味子总木脂素减轻内质网途径凋亡延缓小鼠脑衰老  

Schisandra total lignin attenuates apoptosis of endoplasmic reticulum pathway to delay mouse brain aging

作　　者：于春艳[1] 于春荣 李贺[3] 鞠文博[1] 姜恩平[3,4] 陈建光[3] 

机构地区：[1]北华大学基础医学院,吉林吉林132013 [2]北京昭衍新药研究中心股份有限公司毒理部,北京100176 [3]北华大学药学院,吉林吉林132013 [4]广东医学院,广东东莞523808

出　　处：《中国病理生理杂志》2014年第11期1967-1973,共7页Chinese Journal of Pathophysiology

基　　金：吉林省科技厅自然科学基金资助项目(No.201215103);吉林省教育厅基金资助项目(吉教科合字No.2012394;No.2011130;No.2013194);广东医学院博士启动项目(No.B2012063);吉林市科技计划项目(No.201233122)

摘　　要：目的:利用D-半乳糖复制小鼠衰老模型,探讨北五味子总木脂素(SCL)抗小鼠脑衰老的作用及其作用机制。方法:实验分为空白对照组、模型组以及SCL低、中、高剂量组。小鼠跳台实验检测学习记忆能力,Western blotting方法检测泛素化蛋白(Ub)、葡萄糖调节蛋白78(GRP78)、蛋白质二硫键异构酶(PDI)、C/EBP同源蛋白(CHOP)的表达水平以及线粒体凋亡相关蛋白Bcl-2和Bax表达水平。免疫组化法观察大脑皮质Bcl-2和Bax蛋白表达情况。结果:在学习测试中,模型组小鼠5 min内错误次数较空白对照组增多(P<0.05),SCL低、中、高剂量组小鼠5 min内错误次数均较模型组减少(P<0.05)。在记忆测试中,模型组小鼠首次跳下平台的潜伏期较空白对照组缩短(P<0.05),5 min内错误次数增多(P<0.05);与模型组比较,SCL低、中、高剂量组小鼠首次跳下平台的潜伏期延长(P<0.05),5 min内错误次数减少(P<0.05)。与空白对照组比较,模型组的Ub、GRP78、PDI、CHOP和Bax蛋白表达水平均增加(P<0.05),Bcl-2的蛋白表达水平降低(P<0.05),Bcl-2/Bax比值降低(P<0.05)。与模型组比较,北五味子总木脂素低、中、高剂量组脑组织的Ub、GRP78、PDI、CHOP和Bax蛋白表达水平均降低(P<0.05),Bcl-2的蛋白表达水平升高(P<0.05),Bcl-2/Bax比值升高(P<0.05)。空白对照组神经细胞形态正常,细胞浆的Bcl-2蛋白呈阳性表达,Bax蛋白呈阴性表达;模型组神经细胞变性,细胞浆的Bcl-2蛋白呈阴性表达,Bax呈阳性表达;SCL低、中、高剂量组变性细胞数量均明显减少,细胞浆内的Bcl-2蛋白呈阳性表达,Bax蛋白呈阴性表达。结论:北五味子总木脂素具有抑制D-半乳糖诱导的小鼠脑组织衰老作用,其作用机制与减轻内质网应激途径凋亡有关。AIM： To investigate the role of schisandra total lignin（ SCL） in anti-aging of the mouse brain.METHODS： A D-galactose induced mouse aging model was established. The following groups in this study were set up：control group,model group,SCL low dose group [SCL（ L） ],SCL moderate dose group [SCL（ M） ] and SCL high dose group [SCL（ H） ]. Learning and memory abilities were measured by mouse jumping experiments. The expression of ubiquitin（ Ub）,glucose-regulated protein 78（ GRP78）,protein disulfide isomerase（ PDI）,CCAAT / enhancer-binding protein homologous protein（ CHOP）,Bcl-2 and Bax proteins was detected by Western blotting. In addition,the protein expression of Bcl-2 and Bax in the aging cerebral cortex was also observed by immunohistochemistry. RESULTS： In learning test,compared with control group,the number of errors within 5 min increased in model group（ P〈0. 05）. Compared with model group,the number of errors within 5 min decreased in SCL（ L） group,SCL（ M） group and SCL（ H） group（ P〈0. 05）. In memory test,compared with control group,incubation period of the first jumping off the platform was shorter and the number of errors within 5 min increased in model grou（ P〈0. 05）. Compared with model group,the incubation period of the first jumping off the platform was longer and the number of errors within 5 min decreased in SCL（ L） group,SCL（ M） group and SCL（ H） group（ P〈0. 05）. Compared with control group,the protein expression of Ub,GRP78,PDI,CHOP and Bax was increased（ P〈0. 05）,while Bcl-2 protein level and Bcl-2 / Bax ratio were decreased in model group（ P〈0. 05）. Compared with model group,the protein expression of Ub,GRP78,PDI,CHOP and Bax was decreased in SCL（ L） group,SCL（ M） group and SCL（ H） group（ P〈0. 05）,while Bcl-2 protein level and Bcl-2 / Bax ratio were increased（ P〈0. 05）. In control group,neuronal morphology was normal,the protein expression of Bcl-2 was positive and Bax was negat

关 键 词：北五味子总木脂素 内质网 线粒体 细胞凋亡 衰老 

分 类 号：R363[医药卫生—病理学]