淫羊藿苷延缓衰老过程中对ATM-Chk2-p53通路的调节作用  

The regulating effect of Icariin on ATM-Chk2-p53 pathway in delaying aging

作　　者：陈晓亮[1] 张素琴[2] 

机构地区：[1]杭州师范大学附属医院干部科,浙江省310015 [2]上海市第八人民医院中医科,上海市200235

出　　处：《老年医学与保健》2016年第6期341-344,共4页Geriatrics & Health Care

基　　金：国家自然科学基金(81102681)

摘　　要：目的观察淫羊藿苷对老年小鼠DNA损伤检验点ATM-Chk2-p53通路的调节作用。方法 21月龄C57BL/6老年小鼠随机分为老年对照组和淫羊藿苷组,同时取3月龄小鼠作为青年对照组;淫羊藿苷组小鼠给予含0.02%淫羊藿苷的饲料喂养,老年对照组和青年对照组小鼠给予普通正常小鼠饲料喂养。利用淫羊藿苷干预3个月后,在实验之前部分小鼠先进行5Gy X线照射6 h,然后所有小鼠麻醉后处死,收集标本进行相关实验。取小鼠脾脏,抽提小鼠脾组织中的总RNA,利用Real-time PCR方法检测DNA损伤检验点上关键分子ATM、Chk2和p53的mRNA表达水平;提取小鼠脾组织中的总蛋白,采用Western blot方法检测DNA损伤检验点上p-ATM、p-Chk2和p-p53蛋白的表达。结果在电离辐射情况下,老年小鼠ATM、Chk2和p53基因的mRNA表达的增高倍数明显较青年小鼠低,同时老年小鼠p-ATM、p-Chk2和p53蛋白的表达水平较青年小鼠降低;而淫羊藿苷能够提高老年小鼠在电离辐射情况下ATM、Chk2、p53基因的mRNA表达水平,并且能够提高老年小鼠p-ATM、p-Chk2和p-p53蛋白表达水平。结论淫羊藿苷能够激活DNA损伤检验点ATM-Chk2-p53通路功能,这可能是淫羊藿苷延缓小鼠衰老的重要机制之一。Objective To investigate the regulating effect of icariin on ATM-Chk2-p53 pathway in old mice. Methods c57BL/6 mice of 21 months old were randomly divided into old control group and icariin treated group, and mice of 3 months old were used as young control group; mice in icariin treated group were fed with diet containing 0.02% icariin for 3 months while mice in young and old control groups were fed with the standard mice diet; After 3-month treatment, a half of mice in each group were treated with 5Gy IR for 6 hours and then killed; the mRNA expression of target genes ATM, Chk2, p53 in the spleen were detected by real-time PCR; the protein levels of p-ATM, p-Chk2 and p-p53 in the spleen tissues were measured by western bloting before and after IR. Results The relative induction folds of genes such as ATM, Chk2, and p53 by IR in the spleen of old mice were significantly lower than those in young mice and the protein levels of p-ATM, p-Chk2, p-p53 in spleen tissues after IR in old mice were also much lower than those in young mice; however, icariin could up-regulate the mRNA levels of ATM, Chk2, and p53 genes and protein levels of p-ATM, p-Chk2, p-p53 in old mice treated with IR. Conclusions Icariin could activate the DNA damage checkpoint ATM-Chk2-p53 pathway, which might be an important mechanism of icariin in delaying aging.

关 键 词：衰老 淫羊藿苷 ATM-Chk2-p53通路 

分 类 号：R285[医药卫生—中药学]