3,6-(二甲氨基)-二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响

摘要

目的:观察3,6-(二甲氨基)-二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响.方法:采用牛血清白蛋白(BSA)与不同浓度葡萄糖(0,20,50,80 mmol*L-1)体外孵育制备糖基化终产物(AGEP),应用[3H]-TdR掺入法和MTT比色法观察I-93对重度糖化的AGEP诱导的大鼠主动脉平滑肌细胞(ASMC)增殖的影响;应用放射免疫技术及Greiss法观察I-93对AGEP引起的牛主动脉内皮细胞(BAEC)释放内皮素-1(ET-1)和一氧化氮(NO)的影响.结果:I-93 10-7～10-5mol*L-1能明显抑制AGEP 引起的ASMC增殖,其[3H]-TdR掺入量和MTT比色法的最大抑制率分别为79.4 %和44.2%.随AGEP糖浓度的增加(20～80mmol*L-1),BAEC培养液中ET-1含量亦逐渐上升[(493±63)～(779±105)ng*L-1],I-93 10-7～10-5mol*L-1能明显抑制重度糖化的AGEP促进ET-1释放的作用;I-93对AGEP灭活NO的作用有剂量依赖性抑制效应.结论:I-93有抑制ASMC增殖的作用;对AGEP诱导的BAEC释放ET-1和NO间平衡失调有调节作用,在防治阻塞性血管疾病方面I-93具有潜在的应用价值.%Objective To study effects of 3,6-dimethamidodibenzopyriodonium gluconate (I-93) on advanced glycosylation end products (AGEP)-induced proliferation of rat aortic smooth muscle cells (ASMC) and changes of endothelin (ET) and nitric oxide (NO) of bovine aortic endothelial cells (BAEC).Methods AGEP-BSA was prepared by incubating bovine serum albumin (BSA) with glucose of 0,20,50, 80mmol*L-1 at 37℃.Effect of I-93 on 200 mg*L-1 AGEP-stimulated proliferation of ASMC derived from aorta of Sprague-Dawley rats was studied with [3H]-TdR incorporation and MTT assay.Effects of I-93 on AGEP-induced changes of ET and NO of BAEC derived from calf aorta were observed with radioimmunoassay and Greiss method.Results I-93(10-7～10-5mol*L-1)significantly inhibited AGEP-stimulated proliferation of ASMC in a concentration-dependent manner.AGEP also stimulated ET-1 production of BAEC in a concentration-dependent manner at concentration of glucose from 20 to 80mmol*L-1.The stimulating effect of AGEP on ET-1 production was inhibited by I-93 in a concentration-dependent fashion.The NO content in supernatant medium decreased when the quiescent cultures of BAEC were incubated with AGEP 200mg*L-1 for 12h or 24h.I-93(10-7～10-5mol*L-1)had antagonistic effect on AGEP-induced change of NO of BAEC in a concentration-dependent manner.Conclusions I-93 have effects of inhibiting AGEP-induced proliferation of ASMC and restoring the balance between ET and NO of BAEC.The results suggest that I-93 might have a potential application in the prevention and treatment of occlusive vascular disorders.