摘要
目的探讨GATA-6基因在内源性一氧化碳(CO)抑制肺动脉平滑肌细胞(PVSMCs)增殖中作用。方法体外培养雄性SD大鼠的PVSMCs,用血小板衍生生长因子(PDGF)诱导其增殖,用不同浓度氯血红素(Hemin)诱导血红素加氧酶(HO-1),促进CO生成,用四唑盐(MTT)法测定不同条件下PVSMCs的细胞增殖,氚掺入法测定DNA合成,RT-PCR测定GATA-6基因mRNA的表达。结果CO可抑制PDGF诱导的PVSMCs增殖,此抑制作用呈剂量和时间依赖关系,高浓度Hemin可明显抑制PVSMCs增殖和DNA合成,在PDGF刺激后2 h,PVSMCs的GATA-6表达明显下调,6 h开始恢复,而CO可阻止GATA-6这种下调。结论CO可抑制PDGF诱导的PVSMCs增殖,PDGF可引起GATA-6基因表达下调,这种下调可被CO阻止;提示在抑制PVSMCs异常增殖过程中,CO可能通过调节GATA-6表达发挥作用。
Objective To investigate the effect of GATA - 6 on endogenous carbon monoxide（CO） inhibited pulmonary vascular smooth musele cells（PVSMCs） proliferation induced by platelet - derived growth factor（PDGF）. Methods Tissue mass culture was done to get PVSMCs artery in SD rats. The PVSMCs were stimulated to proliferation by PDGF （20μg/L）,and the 3 different concentrations of hemin[a substrate and inducer of heine oxygenase - 1 （HO - 1） ] add into the cultures to induce CO production. The PVSMC cell proli-feration was detected by 3 - （4,5 - dimethyl - 2 - thiazotyl） - 2,5 - diphenyt - 2H- tetrazolium bromide（MTT） method, DNA synthesis was detected by [^3H] thymidine incorporation,and GATA - 6 mRNA expression was detected by reverse transcription polymerase chain reaction（RT - PCR）. Results CO inhibited the PVSMCs proliferation induced by PDGF in a dose - dependent and time - dependent manner. Hemin with high concentration markedly inhibited the proliferation and DNA synthes-is of PVSMCs. After 2 hours with PDGF, the expression of GATA - 6 mRNA markedly down- regulated,and began returned after 6 hours. However, CO could reversed this down- regulation. Conclusions CO can inhibit the proliferation of PVSMCs induced by PDGF. PDGF can result in the expression of GATA - 6 mRNA down - regulated; the down - regulation is reversed by CO. This study suggested that CO maybe inhibit PVSMCs proliferation by regulating expression of GATA- 6.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2006年第17期1158-1159,1185,共3页
Journal of Applied Clinical Pediatrics
基金
国家自然科学基金项目资助(30300145)
