外源性硫化氢对氧化型低密度脂蛋白诱导组织因子和组织因子途径抑制物表达的影响

Effects of Hydrogen Sulfide on the Expression of Tissue Factor and Tissue Factor Pathway Inhibitor Induced by ox-LDL

目的研究外源性硫化氢对氧化型低密度脂蛋白(ox-LDL)诱导内皮细胞组织因子(TF)和组织因子途径抑制物(TFPI)表达的影响。方法培养人脐静脉内皮细胞(HUVEC),分别以不同浓度NaHS(25、50、100及200μmol/L)和50 mg/L ox-LDL共孵育,RT-PCR和ELISA分别检测TF和TFPI mRNA表达和蛋白含量。结果用50mg/L ox-LDL孵育HUVEC 24 h后,TF mRNA表达上调8倍,蛋白含量增加7倍(P<0.01);而TFPI mRNA表达降低73%,蛋白含量减少65%(P<0.01)。用25、50、100及200μmol/L NaHS预孵育HUVEC 1 h,再与ox-LDL共同孵育,与ox-LDL组相比,加入不同浓度NaHS组TF mRNA分别降低12%、31%、63%和80%(P<0.05),蛋白含量分别降低13%、30%、62%和77%;TFPI mRNA表达分别升高0.6、1.2、2.0和2.6倍,蛋白含量分别升高0.3、0.7、1.1和1.6倍。结论 NaHS能抑制ox-LDL对内皮细胞TF表达的诱导作用,减轻ox-LDL对内皮细胞TFPI表达的抑制作用。

Aim To investigate the effects of hydrogen sulfide （H2S） on oxidized low density lipoprotein （ox- LDL） induced expression of tissue factor （TF） and tissue factor pathway inhibitor （TFPI） in endothelial cells. Meth- ods Human umbilical vein endothelial cells （HUVEC） were cultured and treated with ox-LDL （50 rag/L） in the absence or presence of NariS for 24 h. The mRNA expression and protein content of TF and TFPI in HUVEC were determined by RT-PCR and ELISA, respectively. Results Treatment with ox-LDL for 24 h caused an increased TF mRNA and pro- tein expression by 8 and 7 times, respectively （P 〈0. 01 ）, and a decreased TFPI mRNA and protein expression by 73% and 65% , respectively （P 〈0. 01 ）. However, pretreatment of HUVEC with different concentrations （25, 50, 100 and 200 μmol/L） of NariS （ the donor of H2S） for 1 h before ox-LDL stimulation resulted in a marked inhibition of ox-LDL-in- duced TF mRNA and protein expression by 12%, 31%, 63%, 80% and 13%, 30%, 62%, 77%, respectively （P 〈 0. 05 ） , and an increase of ox-LDL-induced inhibition in TFPI mRNA and protein expression by 0. 6, 1.2, 2. 0, 2. 6 times and 0. 3, 0. 7, 1.1, 1.6 times, respectively （P 〈 0. 05 ）. Conclusion H2 S can inhibit ox-LDL-induced TF expres- sion and increases ox-LDL-inhibited TFPI expression in endothelial cells.