中文摘要：

目的探讨沉默信息调节因子3（SIRT3）参与缺氧预处理保护作用的机制。方法将PCI2细胞分为空白对照组、单纯缺氧预处理组、预处理＋缺氧组、单纯缺氧组。通过噻唑蓝细胞活力测定及DAPI核染色法判定细胞的损伤程度；MitoSOX荧光染色法测定线粒体内活性氧簇的含量；Western Blot测定细胞内SIRT3、过氧化物酶体增生激活受体的共刺激因子-1α（PGC-1α）及锰超氧化物歧化酶（MnSOD）的蛋白表达水平。进一步通过添加重组SIRT3蛋白探讨其与PGC-1α及MnSOD的关系。结果缺氧后细胞的活性减少达51．0％，而预处理＋缺氧组细胞的活力回升至74．7％，4组间细胞活性差异有统计学意义（F=56，P〈0．01）。预处理＋缺氧组活性氧簇含量较缺氧组下降，4组细胞间活性氧簇含量差异有统计学意义（F=318．328，P〈0．01）。4组间SIRT3、PGC-1α及MnSOD的表达差异均有统计学意义（F分别为91．765、302．694、160．480，P均〈0．01），缺氧预处理及缺氧刺激均可上凋3种蛋白的表达，预处理＋缺氧组较缺氧组蛋白表达的增加更明显。添加重组SIRT3蛋白后能上调SIRT3、PGC-1α及MnSOD的蛋白表达，模拟缺氧预处理的保护作用。结论缺氧预处理可产生细胞保护作用，缺氧预处理后SIRT3可能通过PGC-1α上调MnSOD的表达，减少活性氧簇的生成，进而发挥重要的细胞保护作用。

英文摘要：

Objective To investigate the mechanisms underlying neuroprotection of silent information regulation 2 homolog 3 （ SIRT3 ） against hypoxia via preconditioning. Methods PC12 cells were randomly divided into control, hypoxic preconditioning （Hyp） , Hyp with oxygen-glucose deprivation （OGD） and OGD. MTr assay and DAPI staining were used to evaluate cellular viability. MitoSOX Red was used to measure the production of mitochondrial superoxide. The protein expression of SIRT3, PGC-1α and MnSOD were assessed by Western blot. Recombinant SIRT3 was also given to further investigate its roles in bypoxic preconditioning. Results The preconditioned PC12 cells had a higher survival rate. When expressed as a percentage of the control group, MTT values following 6 h OGD were around 51.0% in the OGD group but around 74.7% in the Hyp ＋ OGD group （ F = 56 ,P 〈 0.01 ）. Mitochondrial ROS after Hyp was less than the OGD group. Both Hyp ＋ OGD and OGD increased the expression of SIRT3, PGC-1α and MnSOD proteins, and these increases were greater after Hyp ＋ OGD. Similarly, the application of recombinant SIRT3 to OGD also further increased the expression of these proteins. Conclusions Hypoxic preconditioning can protect PC12 ceils against hypoxic injury. One possible mechanism of hypoxic preconditioning is via SIRT3 to upregulate PGC-1α and, in turn, MnSOD to reduce generation of ROS.