血栓素A2合成酶抑制剂对低氧猪肺动脉平滑肌细胞增殖及凋亡的影响  

Effect of TXA2 inhibitor on the proliferation and apoptosis of hypoxic pulmonary artery smooth muscle cells of porcines

作　　者：丁毅鹏[1] 姚红霞[1] 何海武[2] 石慧芳[2] 林莉[2] 

机构地区：[1]海南省人民医院急救中心,海口 570102 [2]海南省农垦总医院呼吸内科

出　　处：《中华医学杂志》2011年第4期277-281,共5页National Medical Journal of China

基　　金：海南省自然科学基金（2004-396-80464）

摘　　要：目的 探讨血栓素A2（TXA2）合成酶抑制剂奥扎格雷钠对低氧肺动脉平滑肌细胞（PASMC）增殖及凋亡的影响。方法采用四甲基偶氮唑盐微量比色法、免疫组化法及原位末端脱氧核苷酸转移酶标记法观察TXA2激动剂u46619及TXA2合成酶抑制剂奥扎格雷钠对PASMC增殖及凋亡和对反映细胞增殖状态的重要标记物Ki67表达的影响。结果U46619对常氧和低氧PASMC的增殖和低氧PASMC中Ki67的表达均有明显促进作用，并可明显抑制PASMC的凋亡；奥扎格雷钠对常氧PASMC的增殖无明显影响，但对低氧PASMC的增殖和Ki67的表达均有明显抑制作用，可促进低氧PASMC的凋亡；奥扎格雷钠可明显拮抗u46619在常氧和低氧条件下对PASMC的促增殖和Ki67表达的作用，以及u46619抑制低氧PASMC的凋亡的作用。结论奥扎格雷钠有可能通过抑制低氧PASMC的增殖及血管重塑、促进凋亡，从而对低氧性肺动脉高压起治疗作用。Objective To study the effect of Thromboxane A2 （TXA2） inhibitor on the proliferation of hypoxic pulmonary artery smooth muscle cells （PASMC） of poreines. Methods The methods of 3 （4,5- dimethyhhiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT）, immunohistochemistry of Ki67 and TdTmediated dUTP nick end labeling（TUNEL） were employed to measure the proliferation, inhibition rate and apoptosis of PASMC. Results U46619, a thromboxane A2 agonist, could promote the proliferation and expression of Ki67 in PASMC under hypoxic and normal conditions. It could also inhibit the apoptosis of PASMC. Ozagrel, a thromboxane A2 inhibiter, inhibited the proliferation and the expression of Ki67 in PASMC under hypoxia. The inhibition rate was 71.4%, but it had no effect on the proliferation and expression of Ki67 in PASMC under normal conditions. It promoted the apoptosis of PASMC. Ozagrel could inhibit the action of U46619 in promoting the proliferation and expression of Ki67 in PASMC and inhibit the apoptosis of PASMC. Conclusion Ozagrel may be used in treating the pulmonary hypertension by inhibiting the proliferation of PASMC, pulmonary vascular remodeling, and promote the apoptosis of PASMC.

关 键 词：受体 血栓烷A2 前列腺素H2 肺动脉 肌细胞 平滑肌 细胞增殖 细胞 凋亡 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]