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目的:探讨砷诱导内质网应激致肝细胞凋亡过程中微小RNA-153（miR-153）表达变化及调控组蛋白H3第4位赖氨酸（H3K4）甲基转移酶（SET7/9）和组蛋白H3K4一甲基化（H3K4me1）水平变化的机制。方法:体外培养人正常肝细胞（L-02细胞），根据不同处理方式分为对照、砷处理、砷+阴性转染、砷+ miR-153上调和砷+ miR-153下调组，其中砷+阴性转染、砷+ miR-153上调和砷+ miR-153下调组转染质粒与转染试剂均按照3 μg∶8 μl进行转染。24 h后，砷处理、砷+阴性转染、砷+ miR-153上调和砷+ miR-153下调组再以100 μmol/L亚砷酸钠（NaAsOn 2）作为终浓度处理24 h；对照组加入与NaAsOn 2等体积的磷酸盐缓冲液（PBS）处理24 h。采用实时荧光定量PCR（RT-qPCR）检测各组细胞miR-153表达水平；流式细胞术检测各组细胞凋亡和周期情况；实时无标记细胞动态分析（RTCA）仪检测细胞增殖情况；蛋白免疫印迹法（Western blot）检测各组细胞内质网标志蛋白葡萄糖调节蛋白78（GRP78）、SET7/9及H3K4me1蛋白表达水平。n 结果:各组细胞miR-153表达水平比较，差异有统计学意义（n F = 10.73，n P < 0.05）。与对照组[（41.10 ± 6.08）%]比较，砷处理组miR-153表达水平[（4.35 ± 0.20）%]明显降低（ n P < 0.05）；与砷+阴性转染组[（10.00 ± 2.40）%]比较，砷+ miR-153上调组miR-153表达水平[（157.70 ± 42.70）%]明显升高（ n P < 0.05），砷+ miR-153下调组miR-153表达水平[（4.20 ± 0.28）%]明显降低（ n P < 0.05）。各组细胞总凋亡率、G1期细胞比例比较，差异有统计学意义（ n F = 29.69、104.32，n P均< 0.05）。与对照组比较，砷处理、砷+ miR-153上调、砷+ miR-153下调组细胞总凋亡率、G1期细胞比例明显升高（n P均< 0.05）；与砷+阴性转染组比较，砷+ miR-153上调组细胞总凋亡率、G1期细胞比例明显下降（n P均< 0.05），砷+ miR-153下调组细胞总凋亡率、G1期细胞比例明显升高（n P均< 0.05）。各组细胞增殖率比较差异有统计学意义（n F = 799.35，n P < 0.05）。与对照组比较，砷处理、砷+ miR-153上调、砷+ miR-153下调组细胞增殖率明显下降（ n P均< 0.05）；与砷+阴性转染组比较，砷+ miR-153上调组细胞增殖率升高（n P < 0.05），砷+ miR-153下调组细胞增殖率下降（ n P < 0.05）。各组细胞SET7/9、GRP78和H3K4me1蛋白表达水平比较，差异有统计学意义（ n F = 78.52、52.13、54.32，n P均< 0.05）。与对照组比较，砷处理组SET7/9、GRP78和H3K4me1蛋白表达水平明显升高（n P均< 0.05）；与砷+阴性转染组比较，砷+ miR-153上调组SET7/9、GRP78和H3K4me1蛋白表达水平明显下降（n P均< 0.05），砷+ miR-153下调组SET7/9、GRP78和H3K4me1蛋白表达水平明显升高（n P均< 0.05）。n 结论:miR-153在砷诱导内质网应激致肝细胞凋亡过程中具有重要作用，其表达和调控与SET7/9和H3K4me1水平变化有关。“,”Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured n in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO n 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsOn 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1.n Results:The expression levels of miR-153 in each group were significantly different (n F = 10.73, n P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( n P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( n P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( n P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( n F = 29.69, 104.32, n P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( n P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( n P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( n P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( n F = 799.35, n P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( n P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( n P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( n P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( n F = 78.52, 52.13, 54.32, n P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( n P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( n P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( n P < 0.05).n Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.