银杏酮酯抗自然衰老大鼠前额叶皮层氧化DNA损伤和延缓端粒长度的作用及其机制探讨  

The effects of Ginkgo Biloba Extract on anti oxidantive DNA damaging and delaying telomere shortening in prefrontal cortex of natural aging rats and its mechanisms

作　　者：郝莉[1] 任秀花[2] 赵妍[1] 夏趁意[1] 郭晨旭[1] 王艳春[1] 张志雄[1] 

机构地区：[1]上海中医药大学基础医学院生理教研室,上海201203 [2]郑州大学基础医学院解剖教研室,郑州450052

出　　处：《中药药理与临床》2013年第6期38-42,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：上海市科委科研计划项目资助(项目批准号09ZR1432100)

摘　　要：目的:探讨银杏酮酯(GBE50)抗自然衰老大鼠前额叶皮层(prefrontal cortex,PFC)氧化DNA损伤和延缓端粒长度的作用及SIRT1在其中的作用机制。方法:建立自然衰老大鼠模型,用GBE50(100mg/kg)每日灌胃,连续60天。免疫荧光双标观察PFC中8-OHDG的亚细胞定位及表达强度;荧光定量PCR(Real time-PCR)检测PFC全基因组DNA相对端粒长度;Western-blot检测SIRTl、p53和p21的蛋白水平。结果:免疫荧光双标结果显示8-OHDG主要位于PFC神经元胞体中。与青年对照组相比,自然衰老大鼠PFC神经元8-OHDG表达增加,GBE50(100mg/kg)处理后减少。RT-PCR结果显示:与青年对照组相比,自然衰老大鼠PFC相对端粒长度缩短,GBE50(100mg/kg)处理后相对端粒长度缩短延缓。Western blot结果显示:与青年对照组相比,自然衰老大鼠PFC的SIRTl蛋白表达下降,p21蛋白表达增加;GBE50(100mg/kg)处理后自然衰老大鼠PFC的SIRTl蛋白表达增加,p21蛋白表达有下降趋势;而p53蛋白变化不明显。结论:GBE50(100mg/kg)可降低自然衰老大鼠PFC内8-OHDG表达,延缓相对端粒长度缩短,其过程可能与SIRT1、p21蛋白表达有关。Objective： To investigate effects of Ginkgo Biloba Extract （GBE50） on anti oxidantive DNA damaging and telomere length in prefrontal cortex （PFC） of and its mechanism. Method： A natural aging rat model is created and received GBE50 （100mg/kg） by intragastric adminis- tration for 60 days. Immunofluoreseent double staining was used to detect the subeellular localization of 8-OHDG and expression; Real time- PCR was used to measure relative telomere length; Western-blot was used to examine Sirtl, p53 and p21 protein levels. Results： Immunofluorescent double staining confirmed that 8-OHDG was located mainly in the nuclei and the number of 8-OHDG-positive cells was decreased after treated by GBE50 （100mg/kg）（ P 〈 0.05 ）. RT-PCR showed that telomere length decreased after treated by GBE50 （100mg/kg） （P 〈 0.05 ）. Western blot displayed that SIRT1 and p21 decreased and increased, respectively, in PFC of natural aging rats compared with control group （ P 〈 0.05）. The expression of SIRT1 showed a increased tendency （ P 〉 0.05 ）, and there was significant difference in p21 protein level after treated by GBE50 （100mg/kg） （P 〈 0.05 ）. However, the expression change of p53 was not obvious after treated by GBES0 （100mg/kg） （ P 〉 0.05 ）. Conclusion： GBE50 （100mg/kg） might decrease 8-OHDG and delay telomere shortening in the PFC of natural aging rats, and its mechanism might be associated with SIRT1 and p21.

关 键 词：银杏酮酯 自然衰老 前额叶皮层 氧化DNA损伤 SIRT1 

分 类 号：R285[医药卫生—中药学]