H2S通过上调COX-2-PGI2通路拮抗CoCl2诱导的人肺动脉平滑肌细胞过度增殖  

Inhibition of H2S on human pulmonary artery smooth muscle cell excessive proliferation induced by CoCh via up-regulation of COX-2-PGI2 signaling pathway

作　　者：李运泉[1] 林约瑟[1] 李轩狄[1] 方榕[2] 朱玲[1] 王慧深[1] 

机构地区：[1]中山大学附属第一医院心儿科,广州510080 [2]中山大学附属第一医院卫生部辅助循环实验室,广州510080

出　　处：《中华生物医学工程杂志》2013年第2期106-109,共4页Chinese Journal of Biomedical Engineering

基　　金：广东省科技计划项目（20128031800298）

摘　　要：目的 观察硫化氢（H2S）对化学性缺氧诱导的人肺动脉平滑肌细胞（HPASMC）增殖的改善作用并探讨环氧化酶-2（COX-2）在其中的作用.方法 用化学性缺氧模拟剂氯化钴（CoCl2）处理HPASMC,建立缺氧性肺动脉高压的细胞模型.在CoCl2处理前,用硫氢化钠（NaHS,H2S的供体）预处理30 min,检测细胞存活率、胞内COX-2蛋白的表达以及培养基中前列环素（PGI2）的含量.结果 HPASMC经25,50和100 μmol/L的CoCl2处理24h诱导了明显的增殖反应,使细胞增殖率分别提高至（112.7±4.6）％,（116.2±3.3）％和（113.3±4.7）％,与对照组差异有统计学意义（依次P＜0.05,0.01和0.05）.用50μmol/L CoCl2处理18～24 h,时间依赖性地诱导HPASMC增殖（R为0.99）.50 μmol/LCoCl2处理HPASMC 24 h可明显下调胞内COX-2蛋白的表达（P＜0.05）并抑制细胞释放PGI2 （P＜0.05）.外源性地给予PGI2可使CoCl2诱导的细胞增殖率约降低9％,二者差异有统计学意义（P＜0.05）.在用50 μmol/L CoCl2处理HPASMC前,给予400 μmol/L NaHS预处理30 min,也可使CoCl2的致增殖效应明显减弱（P＜0.05）,另外,NaHS预处理还使胞内COX-2的蛋白表达从0.17±0.08提高至0.59±0.21,并将细胞释放PGI2能力提高2倍.结论 H2S可改善缺氧诱导的HPASMC过度增殖,其分子机制与上调COX-2-PGI2通路的表达有关.Objective To investigate the effects of hydrogen sulfide （HzS） on excessive proliferation of human puhnonary artery smooth muscle cells （HPASMC） induced by chemical hypoxia and to explore the role of eyclooxygenase-2 （COX-2）. Methods HPASMCs were treated with COCl2, a hypoxia- mimicking agent, to establish a cellular model of hypoxie pulmonary arterial hypertension （PAH）. Prior to the treatment with CoCl2, HPASMCs were preconditioned with sodium hydrosulfide （NariS）, a donor of H2S, for 30 minutes. Cell viability, intracellular expression of COX-2 and the level of PGI2 in culture medium were assayed. Results Exposure of HPASMCs to COC12 at the concentrations of 25, 50 and 100 μmol/L for 24 hours markedly induced cellular proliferation, with the ratio of （112.7±4.6） % （P〈0.05）, （ 116.2±3.3 ） % （P〈 0.01 ） and （113.3±4.7）% （P〈0.05） compared with control group. Treatment of HPASMC with 50 μmol/L CoCI2 for 18 to 24 hours promoted cellular proliferation in a time-dependent manner （R=0.99）. Treatment with 50 μmol/L COC12 for 24 hours significantly attenuated intraeellular COX-2 expression and PGI2 secretion from HPASMCs （both P〈0.05）, whilst exogenous administration of PGI2 considerably reduced CoCl2-induced cellular proliferation by 9% （P〈0.05）. Preconditioning of HPASMCs with 400 μmol/L Naris for 30 minutes markedly attenuated cellular proliferation induced by COC12 （P〈0.05） , promoted COX-2 expression from 0.17±0.08 to 0.59±0.21 and resulted in a 2-fold increase in PGI2 secretion. Conclusion H25 can ameliorate hypoxia-induced cellular proliferation possibly related to the up-regulation of COX-2-PGI2 signaling pathway.

关 键 词：硫化氢 高血压 肺性 环氧化酶2 依前列醇 

分 类 号：R544[医药卫生—心血管疾病]