摘要目的:探讨组蛋白去乙酰化酶抑制剂曲古霉素A(TSA)对脂多糖(LPS)诱导的人微血管内皮细胞(HMEC)损伤和凋亡的影响。方法:以HMEC为实验细胞，建立LPS诱导的脓毒症细胞模型，根据处理方式不同分为3组：空白对照组(加入磷酸盐缓冲液150 μL)、LPS处理组(加入5 μg/mL的LPS 150 μL)、LPS+TSA干预组(加入5 μg/mL的LPS和500 μg/L的TSA 150 μL)。各组细胞处理后继续培养24 h和48 h，ELISA法检测细胞培养液上清中乳酸脱氢酶(LDH)浓度并使用流式细胞术检测细胞凋亡程度，进行组间比较。结果:与空白对照组比较，LPS处理组LDH浓度在24 h[(4.67±1.27)ng/L比(11.57±0.83)ng/L]和48 h[(7.93±0.80)ng/L比(12.72±0.89)ng/L]显著升高；与LPS处理组比较，LPS+TSA干预组LDH浓度在24 h[(6.01±0.29)ng/L]和48 h[(5.96±0.27)ng/L]明显下降，差异均有统计学意义( P<0.05)。与空白对照组相比，LPS处理组HMEC细胞凋亡率在24 h[(0.92±0.89)%比(1.66±0.09)%]和48 h[(1.09±0.14)%比(5.01±0.16)%]明显升高；与LPS处理组比较，LPS+TSA干预组HMEC细胞凋亡率在24 h[(1.36±0.01)%]和48 h[(4.19±0.23)%]有所下降，差异均有统计学意义( P<0.05)。 结论:TSA在脓毒症中具有降低细胞损伤和减少细胞凋亡的保护作用。

abstractsObjective:To investigate the effect of histone deacetylase inhibitor trichostatin A(TSA) on the lipopolysaccharide(LPS)-induced injury and apoptosis of human microvascular endothelial cell(HMEC).Methods:HMECs were used as research cells to establish LPS-induced septic cell model, which were divided into three groups according to different treatments: control group (150 μL of phosphate buffer), LPS group (150 μL of 5 μg/mL LPS), LPS+ TSA group (150 μL of 5 μg/mL LPS and 500 μg/L TSA). After cells of each group were cultured for 24 h and 48 h, the concentration of lactate dehydrogenase(LDH)in the culture supernatant was detected by enzyme-linked immunosorbent assay and the apoptosis rate of HMECs was detected by Annexin V-FTTC/PI staining, then comparison between different groups were made.Results:Compared with the control group, LDH concentration in LPS group increased significantly at 24 h[(4.67±1.27) ng/L vs. (11.57±0.83) ng/L ] and 48 h[(7.93±0.80) ng/L vs. (12.72±0.89) ng/L ]; Compared with LPS group, LDH concentration in LPS + TSA group decreased significantly at 24 h[(6.01±0.29) ng/L ] and 48 h[(5.96±0.27) ng/L ], and the differences were statistically significant ( P<0.05). Compared with the control group, the apoptosis rates of HMEC cells in LPS group were significantly higher at 24 h[(0.92±0.89)% vs. (1.66±0.09)% ] and 48 h[(1.09±0.14)% vs. (5.01±0.16)%]; Compared with LPS group, the apoptosis rate of HMEC cells in LPS + TSA group significantly decreased at 24 h[(1.36±0.01)% ] and 48 h[(4.19±0.23)% ], the differences were statistically significant ( P<0.05). Conclusion:TSA has the protective effect of reducing cell injury and apoptosis in sepsis.