新型磺酰脲类化合物G004对血管内皮细胞的保护作用

目的: 探讨新型磺酰脲类化合物G004对血管内皮细胞的保护作用。方法: 采用H2O₂造ECV304细胞氧化损伤模型,考察C004对细胞活力、丙二醛(MDA)、超氧化物歧化酶(SOD)以及G004对大鼠血浆中活性氧(ROS)的影响;皮下注射盐酸肾上腺素结合冰泳复制大鼠血管内皮细胞损伤模型,检测G004对血小板聚集率、组织纤溶酶原激活剂(t-PA)、组织纤溶酶原激活抑制剂(PAI)、F-6-酮-前列腺素F_1a(6-K-PGF_1a)、 血栓烷B₂(TXB₂)分泌的影响;股静脉注射组胺复制大鼠血管内皮损伤模型,考察G004对动脉璧摄取伊文思蓝及血浆GMP140含量的影响,结果:G004可明显改善氧化损伤的ECV304细胞形态学变化,提高活细胞比率,降低MDA含量,提高SOD的活力,降低大鼠血浆ROS 的含量;G004升高肾上腺素加冰泳刺激的大鼠血桨6-keto-PGF_1a、t-PA含量,而且降低TXB₂、PAI水平以及血小板聚集率;G004降低组胺所致内皮损伤大鼠的动脉壁伊文思蓝摄取量、降低血浆CMP140的含量,并呈剂量依赖性。结论: G004 清除氧自由基,保护血管内皮的完整性,调节受损内皮细胞分泌TXA₂、PGI₂、t-PA、PAI,抑制GMP140的升高,G004对血管内皮具有较好的保护作用、

Protective effects of G004 on vascular endothelial cells

AIM: To study the protective effects of a novel sulfonylureous compound 1-[4-[2-(4-bromobenze-nesulfonaminoethyl) phenylsufonyl]-3-(trans-4-methylcyclohexyl) urea, G004, on vascular endothelial cells.METHODS: They were determined for the effects of compound G (04 on cell viability, concentration of malon-dialdehyde (MDA, a main decomposed product in lipicperoxidation) and activity of superoxide dismutase (SODin supernatant of oxidative injury endothelial cell(ECV304) of human umbilical vein caused by hydrogen peroxide. The activity of reactive oxygen species (ROS)in rat blood plasma was examined. The mode of vascularendothelial cell injury in rats was established by a higdose of adrenaline in combination with cold-water irritation. Then, the influence of compound GOO4 on plateletaggregation, the content of 6-K-PGENA, TXB2 T-PA, PATin blood plasma was investigated. The permeability of Evans blue in aortic wall and the blood plasma content ofGMP140 were studied in rats with injured vascular endothelial cell resulted from histamine.RESULTS: The compound C004 significantly improved the structuralchange of ECV304 cells damaged by hydrogen peroxidele prodt of MDA, increased activity ofSOD and the rate of animate cells. The compounreduced the production of ROS in the blood plasma ofrats. Compound G% 04 not only enhanced PGL] T-PA re-lease but reduced TXA2 PAI and potently inhibitedplatelet aggregation. The compound G004 decreasedGMP140 secretion from endothelial cells and permeability of Evans blue through aortic wall in rats injured by hista-mine with dose-dependence.CONCLUSION: The com-pound G004 can maintain the integrity of vascular endo-thelia cells, remove the ROS, modulate the secretion of TXA2, PGI2,, t-PA, PAL derived from endothelial cells and inhibit the increase of GMP140. The compound G004 shows the protective effect on vascular endothelial cell.