老年大鼠海马炎性衰老相关基因表达及淫羊藿苷对其影响  

Inflamm-aging related genes expressions in aged rat hippocampus and Icariin intervention outcome

作　　者：夏世金[1] 沈自尹[2] 董竞成[2] 刘小雨[3] 黄建华[2] 汪海东[1] 吴斌[2] 陈伟华[2] 

机构地区：[1]复旦大学附属华东医院,上海市老年医学研究所,上海200040 [2]复旦大学附属华山医院中西医结合研究所,上海200040 [3]同济大学附属第十人民医院中医科,上海200072

出　　处：《老年医学与保健》2008年第6期340-344,347,共6页Geriatrics & Health Care

基　　金：国家重点基础研究发展计划（973项目,编号：2007CB507400）

摘　　要：目的 探讨炎性衰老的炎性细胞因子网络机制，及淫羊藿苷（Icariin，Ica）干预的效果与机制。方法清洁级健康雄性SD大鼠30只，随机等分为4月龄（4m）、24月龄（24m）和24月龄加Ica干预（24m＋Ica）三组。自21月龄满开始，24m＋Ica组予Ica灌胃，24m组给予等量蒸馏水灌胃，均连续90d。取各组大鼠海马组织，应用炎症细胞因子与受体基因芯片进行基因表达检测，绘制基因表达谱，筛选有表达差异的基因。海马组织匀浆，离心取上清液，运用酶联免疫吸附法检测上清液中炎性细胞因子TNF-α、IL-6和IL-10蛋白表达。结果在海马组织中，与4m组相比，24m组表达卜调的促炎性反应细胞因子与受体基因有9个，表达下调的抗炎细胞因子与受体基因有6个。与24m组比较，24m＋Ica组中表达上调的抗炎细胞凶子与受体基因有6个，下调的促炎细胞因子与受体基因有9个。24m组海马组织中TNF-α和IL-6蛋白水平都显著高于4m组（P〈0，01）；与24m组比较，24m＋Ica组中TNF-α和IL-6蛋白水平都明显降低，IL-1蛋白水平显著升高（P〈0．01）。与4m组相比，24m组海马组织上清液中TNF-α／IL-10和IL-6／IL-10比值均显著升高（P〈0．01）；24m＋Ica组TNF-α／IL-10和IL-6／IL-10比值均比24m组显著降低（P〈0．01）。结论 老年大鼠海马存在促炎性细胞因子基闪表达上调，导致促航炎性细胞因子网络和促-抗炎反应体系平衡失调，这可能是炎性衰老中出现高促炎性反应状态的原因和炎性衰老发生的新机制；Ica可能通过下调促炎性细胞因子基因表达和上调抗炎性细胞因子基因表达，重塑促-抗炎性细胞因子网络和促-抗炎性反应体系新的平衡来干预炎性衰老。Objective This work was to study mechanisms of the inflammatory cytokine network in the development of inflamm-aging and the effect and mechanism of Icariin （Ica） on it. Methods Healthy male Sprague Dawley rats were divided into 3 groups （10 rats each group）： 4m group with 4 months rats, 24m group with 24 months rats with distilled water intragastric administration and 24m＋Ica group with 24 months rats treated with Ica by intragastric administration for 3 months from 21 months. Gene expression profiles of rat hippocampal tissues from each group were analyzed by using inflammatory cytokines and receptors cDNA microarrays. Differentially expressed genes were screened. At the same time, inflamm-aging-related inflammatory cytokine protein expression levels of TNF-α, IL-6 and IL-10 in rat hippocampal tissues were evaluated by Enzyme Linked Immunosorbent Assay. Results Compared with 4m group, there were 9 differentially up-regulated expressed pro-inflammatory genes and 6 down-regulated expressed anti-inflammatory genes in rat hippocampal tissues of 24m group. Compared with 24m group, there were 6 up-regulated expressed anti-inflammatory genes and 9 down-regulated expressed pro-inflammatory genes in 24m＋Ica group. Compared with 4m group, protein levels of TNF-α and IL-6 in the supernatant from rat hippocampal tissues of 24m group increased significantly （P 〈0.01）. Compared with 24m group, protein levels of TNF-α and IL-6 in the supernatant from rat hippocampal tissues of 24m＋Ica group decreased significantly （P 〈0.01）, while protein level of IL-10 in 24m＋Ica group was significantly higher than that in 24m group （P 〈 0.01）. The ratio of TNF-α to IL-10 and IL-6 to IL-10 in 24m group increased significantly compared with that in 4m group （P 〈0.01）, and decreased significantly in 24m＋Ica group compared with that in 24m group （P〈0.01）.Conclusions Genes expressions of pro-iinflammatory cytokines and receptors are upregulated in the hippocampus of aged rat, which may eventu

关 键 词：炎性衰老 寡核苷酸序列分析 酶联免疫吸附测定 肿瘤坏死因子α 白细胞介素10 白细胞介素6 海马 大鼠 淫羊藿甙 

分 类 号：R339.38[医药卫生—人体生理学]