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目的:探讨组蛋白脱乙酰酶6（HDAC6）抑制剂Tubastatin A对人皮肤成纤维细胞（HSF）增殖及运动性的影响及其可能的分子机制。方法:采用实验研究方法。取对数生长期HSF，按随机数字表法分为阴性对照组及1 μmol/L Tubastatin A组、5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组。阴性对照组加入含终体积分数0.1%二甲基亚砜的DMEM培养液（以下简称完全培养液），其余3组分别加入含相应终物质的量浓度Tubastatin A的完全培养液。常规培养24 h后，采用细胞计数试剂盒8（CCK-8）法和5-乙炔基-2\'-脱氧尿嘧啶核苷（EdU）染色检测细胞增殖活力；在活细胞工作站下观察细胞3 h内运动范围，计算细胞曲线运动速度；采用蛋白质印迹法检测胞外信号调节激酶1/2（ERK1/2）及磷酸化ERK1/2（p-ERK1/2）的蛋白表达量，并计算p-ERK1/2与ERK1/2比值，以此表示ERK1/2活性。CCK-8法行细胞增殖活力检测样本数为6，其余实验样本数为3。对数据行单因素方差分析及LSD检验。结果:培养24 h后，CCK-8法和EdU染色显示，与阴性对照组比较，1 μmol/L Tubastatin A组、5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组细胞增殖活力均显著下降（n P<0.01）。培养24 h后，CCK-8法显示，与1 μmol/L Tubastatin A组比较，10 μmol/L Tubastatin A组细胞增殖活力显著下降（n P<0.05）；EdU染色显示，与1 μmol/L Tubastatin A组比较，5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组细胞增殖活力显著下降（n P<0.05或n P<0.01）。观察3 h内，1 μmol/L Tubastatin A组、5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组细胞运动范围较阴性对照组明显缩小。观察3 h内，阴性对照组细胞曲线运动速度为（0.780±0.028）μm/min，明显快于1 μmol/L Tubastatin A组、5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组细胞的（0.594±0.023）、（0.469±0.028）、（0.391±0.021）μm/min（n P<0.01）；1 μmol/L Tubastatin A组细胞曲线运动速度明显快于5 μmol/L Tubastatin A组和10 μmol/L Tubastatin A组（n P<0.01）；5 μmol/L Tubastatin A组细胞曲线运动速度明显快于10 μmol/L Tubastatin A组（n P<0.05）。培养24 h后，与阴性对照组比较，1 μmol/L Tubastatin A组、5 μmol/L Tubastatin A组、10 μmol/L Tubastatin A组细胞ERK1/2的活性显著下降（n P<0.01）；与1 μmol/L Tubastatin A组比，5 μmol/L Tubastatin A组和10 μmol/L Tubastatin A组细胞ERK1/2的活性显著下降（n P<0.01）；与5 μmol/L Tubastatin A组比较，10 μmol/L Tubastatin A组细胞ERK1/2的活性显著下降（n P<0.05）。n 结论:HDAC6抑制剂Tubastatin A可能通过抑制ERK1/2活性，从而抑制HSF增殖及运动。“,”Objective:To explore the effects and possible molecular mechanism of histone deacetylase 6 (HDAC6) inhibitor Tubastatin A on the proliferation and movement of human skin fibroblasts (HSFs).Methods:The experimental research method was used. HSFs in logarithmic growth phase were taken and divided into negative control group, 1 μmol/L Tubastatin A group, 5 μmol/L Tubastatin A group, and 10 μmol/L Tubastatin A group according to the random number table. The HSFs in negative control group were added with Dulbecco′s modified eagle medium with the final volume fraction of 0.1% dimethyl sulfoxide (hereinafter referred to as the complete medium), and the other three groups were added with the complete medium with the corresponding final molarity of Tubastatin A. After 24 h of conventional culture, the cell proliferation activity was detected using cell counting kit 8 (CCK-8) method and 5-ethynyl-2\'-deoxyuridine (EdU) staining; the range of motion of cells within 3 h was observed under the living cell workstation, and the curve movement velocity of the cells was calculated. The protein expressions of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting, and the ratio of p-ERK1/2 to ERK1/2 was calculated to represent the activity of ERK1/2. The sample number in cell proliferation activity detection with CCK-8 method was 6, while the sample numbers in other experiments were 3. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:After 24 h of culture, CCK-8 method and EdU staining showed that compared with negative control group, the cell proliferation activities in 1 μmol/L Tubastatin A group, 5 μmol/L Tubastatin A group, and 10 μmol/L Tubastatin A group were significantly decreased (n P<0.01). After 24 h of culture, CCK-8 method showed that compared with 1 μmol/L Tubastatin A group, the cell proliferation activity in 10 μmol/L Tubastatin A group was significantly decreased (n P<0.05); EdU staining showed that compared with 1 μmol/L Tubastatin A group, the cell proliferation activities in 5 μmol/L Tubastatin A group and 10 μmol/L Tubastatin A group were significantly decreased (n P<0.05 orn P<0.01). Within 3 h of observation, the ranges of cell motion in 1 μmol/L Tubastatin A group, 5 μmol/L Tubastatin A group, and 10 μmol/L Tubastatin A group were obviously reduced compared with that in negative control group. Within 3 h of observation, the curve movement velocity of cells in negative control group was (0.780±0.028) μm/min, which was obviously faster than (0.594±0.023), (0.469±0.028), and (0.391±0.021) μm/min of 1 μmol/L Tubastatin A group, 5 μmol/L Tubastatin A group, and 10 μmol/L Tubastatin A group (n P<0.01); the curve movement velocity of cells in 1 μmol/L Tubastatin A group was obviously faster than those in 5 μmol/L Tubastatin A group and 10 μmol/L Tubastatin A group (n P<0.01); the curve movement velocity of cells in 5 μmol/L Tubastatin A group was obviously faster than that in 10 μmol/L Tubastatin A group (n P<0.05). After 24 h of culture, compared with negative control group, the activities of ERK1/2 of cells in 1 μmol/L Tubastatin A group, 5 μmol/L Tubastatin A group, and 10 μmol/L Tubastatin A group were decreased significantly (n P<0.01); compared with 1 μmol/L Tubastatin A group, the activities of ERK1/2 of cells in 5 μmol/L Tubastatin A group and 10 μmol/L Tubastatin A group were decreased significantly (n P<0.01); compared with 5 μmol/L Tubastatin A group, the activity of ERK1/2 of cells in 10 μmol/L Tubastatin A group was decreased significantly (n P<0.05).n Conclusions:HDAC6 inhibitor Tubastatin A may mediate the inhibitory effect on proliferation and movement of HSFs by inhibiting the activity of ERK1/2.