The role of cytokines on the production of NO and PGI2 by human pulmonary artery smooth muscle and endothelial cells

采用尸体解剖材料培养人肺动脉平滑肌细胞（HAPSMC），观察脂多糖（LPS）和细胞因子对PGI_2生成和花生四烯酸代谢的影响。1) LPS、IL-1_< β >和TNF_< α >对PGI_2和一氧化氮（NO）的生成均有促进作用。2)HPLC分析表明，10mug/ml LPS和200U/ml IL-1_< β >对脂氧合酶（LO）和环氧合酶（COX）产物的生成均有促进作用，500U/ml TNFalpha对COX产物的生成均有促进作用。3) IL-6抑制了HPASMC产生PGI_2的基础，并减弱了LPS、IL-1_< β >或TNF_< α >对HPASMC产生PGI_2的促进作用。4)LPS、IL-1_< β >联合NO合酶抑制剂L-NMMA对HPASMC产生PGI_2的促进作用减弱。5) LPS或IL-1_< β >联合硝普钠、NO供体对HPASMC细胞PGI_2生成的促进作用增强，IL-1_< β >对PGI_2生成的促进作用增强。6)以上实验结果表明：(1)人肺动脉平滑肌细胞在LPS或细胞因子作用下可产生NO和PGI_2。(2) NO可促进肺动脉平滑肌细胞生成PGI_2。(3)肺动脉平滑肌细胞可通过生成NO和PGI_2，积极参与肺血流和肺动脉张力的调节。NO促进PGI_2生成的机理有待进一步研究。

Human pulmonary artery smooth muscle cells (HAPSMC) were cultured from autopsy materials, and the effect of lipopolysaccharide (LPS) and cytokines on PGI_2 production and arachidonic acid metabolism by HPASMC was examined.1) LPS,IL-1_<beta> and TNF_<alpha> enhanced the production of PGI_2 and nitric oxide (NO) by HPASMC.2) HPLC analysis revealed that 10mug/ml of LPS and 200U/ml of IL-1_<beta> enhanced the production of both lipoxygenase (LO) and cyclooxygenase (COX) products, and 500U/ml of TNFalpha enhanced that of COX products.3) IL-6 suppressed the basal production of PGI_2 by HPASMC,and attenuated the enhancement of PGI_2 production by HPASMC treated with LPS,IL-1_<beta> or TNF_<alpha>.4) The enhancement of PGI_2 production by LPS and IL-1_<beta> was attenuated when HPASMC were treated with LPS or IL-1_<beta> together with L-NMMA,NO synthase inhibitor.5) The enhancement of PGI_2 production by LPS and IL-1_<beta> was augmented when HPASMC were treated with LPS or IL-1_<beta> together with sodium nitroprusside, NO donor.6) From these experimental findings, it is suggested that(1) Human pulmonary artery smooth muscle cells could produce NO and PGI_2 in response to LPS or cytokines.(2) NO could enhance the production of PGI_2 by pulmonary artery smooth muscle cells(3) Pulmonary srtery smooth muscles could actively participate in the regulation of pulmonary blood flow and tonus of pulmonary artery by producing NO and PGI_2.Further examination is needed to elucidate the mechanism of the enhancement of PGI_2 production by NO.