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目的:探讨瑞芬太尼对缺氧/复氧诱导的PC12细胞增殖、凋亡和氧化应激的影响及分子机制。方法:将PC12细胞按照随机数字表法分为缺氧/复氧组（缺氧15 h后复氧5 h），空白组（正常培养的细胞），瑞芬太尼低、中、高浓度组（2、10、50 mg/L瑞芬太尼处理缺氧/复氧诱导的PC12细胞），瑞芬太尼+LY294002组（10 mg/L的瑞芬太尼和50 μmol/L的LY294002处理缺氧/复氧诱导的PC12细胞），瑞芬太尼+PBS组（10 mg/L的瑞芬太尼和等量的磷酸盐缓冲液处理缺氧/复氧诱导的PC12细胞）（每组9孔）。Western blot法检测各组细胞周期蛋白D1（Cyclin D1）、活化的含半胱氨酸的天冬氨酸蛋白酶-3（cleaved cysteinyl aspartate specific proteinase-3, cleaved caspase-3）、B淋巴细胞瘤-2相关X蛋白（B-cell lymphoma-2 related X protein, Bax）、B淋巴细胞瘤-2（B-cell lymphoma-2, Bcl-2）、磷酸化蛋白激酶B（phosphorylated protein kinase B, p-Akt）、磷酸化雷帕霉素靶蛋白（phosphorylated mammalian target of rapamycin, p-mTOR）和磷酸化信号转导和转录激活因子3（phosphorylation signal transduction and transcriptional activator 3, p-STAT3）蛋白水平；四甲基偶氮唑盐比色法（tetramethylazozolium salt colorimetric assay, MTT）检测细胞存活率，流式细胞术检测细胞凋亡；活性氧（reactive oxygen species, ROS）试剂盒、超氧化物歧化酶（superoxide dismutase, SOD）试剂盒分别检测空白组、缺氧/复氧组和瑞芬太尼低、中、高浓度组ROS水平和SOD活性；ELISA法检测各组IL-1β和TNF-α水平。结果:与空白组比较：缺氧/复氧组PC12细胞的Cyclin D1、Bcl-2、p-Akt、p-mTOR、p-STAT3、SOD及细胞存活率明显降低，cleaved caspase-3、Bax、IL-1β、TNF-α、细胞凋亡率及ROS荧光强度明显升高（n P<0.05）。与缺氧/复氧组比较：瑞芬太尼低、中、高浓度组PC12细胞的Cyclin D1、Bcl-2、p-Akt、p-mTOR、p-STAT3、细胞存活率及SOD活性明显升高，cleaved caspase-3、Bax、IL-1β、TNF-α、细胞凋亡率及ROS荧光强度明显降低（n P<0.05）。与瑞芬太尼+PBS组比较：瑞芬太尼+LY294002组PC12细胞的cleaved caspase-3、Bax、IL-1β、TNF-α及细胞凋亡率明显升高，Bcl-2、p-Akt、p-mTOR、p-STAT3蛋白水平及细胞存活率明显降低（n P<0.05）。n 结论:瑞芬太尼可促进PC12细胞增殖，抑制缺氧/复氧诱导的细胞凋亡、氧化应激和炎症因子的分泌，其机制可能与蛋白激酶B/哺乳动物雷帕霉素靶蛋白/信号转导和转录激活因子3（protein kinase B/mammalian target of rapamycin/signal transducers and activators of transcription 3, Akt/mTOR/STAT3）信号通路有关。“,”Objective:To investigate the effects of remifentanil on the proliferation, apoptosis and oxidative stress of PC12 cells induced by hypoxia/reoxygenation and related molecular mechanisms.Methods:According to the random number table method, PC12 cells were divided into the following groups (n n=9): a hypoxia/reoxygenation group (hypoxia for 15 h followed by reoxygenation for 5 h), a blank group (normally cultured cells), remifentanil low, medium and high concentration groups (PC12 cells exposed to 2, 10, and 50 mg/L remifentanil after hypoxia/reoxygenation induction), a remifentanil+LY294002 group (PC12 cells exposed to 10 mg/L remifentanil and 50 μmol/L LY294002 after hypoxia/reoxygenation induction), and a remifentanil+PBS group (PC12 cells exposed to 10 mg/L remifentanil and an equal amount of phosphate buffer saline after hypoxia/reoxygenation induction). The levels of cyclin D1, cleaved cysteinyl aspartate specific proteinase-3 (cleaved caspase-3), B-cell lymphoma-2 related X protein (Bax), B-cell lymphoma-2 (Bcl-2), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylation signal transduction and transcriptional activator 3 (p-STAT3) were detected by Western blot. The cell viability was measured by tetramethylazozolium salt colorimetric assay (MTT) assay. The apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) kits and superoxide dismutase (SOD) kits were used to detect ROS levels and SOD activity in the blank group, the hypoxia/reoxygenation group, and the remifentanil low, medium, and high concentration groups, respectively. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immuno sorbent assay (ELISA).n Results:Compared with the blank group, the levels of cyclin D1, Bcl-2, p-Akt, p-mTOR and p-STAT3, SOD activity and cell survival rate in the hypoxia/reoxygenation group significantly decreased; and the levels of cleaved caspase-3, Bax, IL-1β and TNF-α, cell apoptosis rate and ROS fluorescence intensity in the hypoxia/reoxygenation group significantly increased (n P<0.05). Compared with te hypoxia/reoxygenation group, the levels of cyclin D1, Bcl-2, p-Akt, p-mTOR and p-STAT3, cell survival rate and SOD activity in PC12 cells in the remifentanil low, medium and high concentration groups significantly increased; and the levels of cleaved caspase-3, Bax, IL-1β and TNF-α, cell apoptosis rate and ROS fluorescence intensity significantly decreased (n P<0.05). Compared with the remifentanil+PBS group, the levels of cleaved caspase-3, Bax, IL-1β and TNF-α, and apoptosis rate in the remifentanil+LY294002 group significantly increased; and the levels of Bcl-2, p-Akt, p-mTOR and p-STAT3 and cell survival rate significantly decreased (n P<0.05).n Conclusions:Remifentanil can stimulate the proliferation of PC12 cells, inhibit hypoxia-reoxygenation-induced apoptosis, oxidative stress and the secretion of inflammatory factors, which may be related to the protein kinase B/mammalian target of rapamycin/signal transducers and activators of transcription 3 (Akt/mTOR/STAT3) signaling pathway.