中文摘要：

目的检测体外培养的人胚肺成纤维细胞复制性衰老过程中及过氧化氢诱导细胞早衰阶段P66Shc启动子区的组蛋白修饰变化。方法按传代情况将人胚肺成纤维细胞分为年轻细胞（22 population doubling levels，22PDL）组、中年细胞（35PDL）组、复制性衰老细胞（49PDL）组和氧化应激诱导的早衰细胞（prematurese Heseenee，PS）组。检测P66Shc的mRNA表达及其启动子区IP1、IP2组蛋白修饰，包括组蛋白H3、H4乙酰化和H3（Lys4）甲基化修饰。结果与年轻细胞组比较，中年细胞组、复制性衰老细胞组和早衰组人胚肺成纤维细胞P66Shc mRNA表达水平均升高，差异有统计学意义（P〈0．05，P〈0．01）。在P66SheIP1启动子区（-1641～1392bp），中年细胞组和复制性衰老细胞组以H4乙酰化修饰为主，而早衰细胞组受H3、H4乙酰化和H3（Lys4）甲基化的联合修饰；在P66Shc IP2启动子区（-129～45bp），中年细胞组和复制性衰老细胞组受H3（Lys4）甲基化修饰，而早衰细胞组受H4乙酰化和H4（Lys4）甲基化联合修饰。结论在细胞衰老过程中，P66Shc启动子区的组蛋白修饰参与其mRNA表达调控，复制性衰老与早衰的调控机制存在差异。

英文摘要：

Objective To detect the alterations of histone modifications for P66Shc promoter during cellular replicative senescence and premature senescence induced by hydrogen peroxide（H202） of human embryonic lung fibroblasts（HEFs） in vitro. Methods The HEFs were divided into young cells（22 population doubling levels, 22PDL）, midaged cells（35PDL） and replicative senescent cells（49PDL） and premature senescent ceils induced by H202（premature senescence, PS） according to the age definition in cell culture. The mRNA level of P66Shc and its histone modifications in the promoter were detected,including acetylation for H3, H4 and methylation for H3（Lys4）. Results The mRNA levels of P66Shc of HEFs increased in mid-aged cells, replicative senescence cells and premature senescent cells with significantly statistical difference（P〈0.05, P〈0.01） compared with those of young cells. In the promoter （-1 641-1 392 bp） of P66Shc IP1, the main histone modification was H4 alteration for both mid- aged and replicative senescent cells,while H3,H4 acetylation and H3Lys4 methylation jointly for premature senescent cells. In the region（-129-＋45 bp） of IP2,the main histone modification was H3 Lys4 methylation for both mid-aged and replicative senescent cells, while H4 acetylation and H3Lys4 methylation combinedly for premature senescent cells. Conclusion The histone modifications in the promoter region take part in regulating the mRNA expression for P66Shc during cellular senescence and different mechanisms exist between replicative and premature senescence.