【摘要】 目的:研究尾加压素Ⅱ(UⅡ)对肾系膜细胞(GMC)增殖功能的影响以及细胞内信号转导机制。方法:①采用[3H]-胸腺嘧啶(3H-TdR)掺入实验研究UⅡ对GMC增殖的影响。②加入不同的细胞内信号转导阻断剂,观察UⅡ作用的信号转导通路。结果:UⅡ以浓度[(10-9～10-7)mol/L]依赖的方式促进GMC3H-TdR掺入,分别较对照组高86.9%、105.8%和134.2%(P<0.01)。UⅡ刺激3H-TdR掺入的效应能够被L-钙通道阻断剂尼卡地平、钙调素激酶(CaM-PK)阻断剂W7和蛋白激酶C(PKC)阻断剂H7所抑制,抑制率分别为42.3%、49.3%和34.1%(P<0.01)。丝裂素活化蛋白激酶阻断剂PD98059虽能轻度抑制UⅡ效应,但无统计学意义(P>0.05)。结论:UⅡ明显促进GMC增殖,该效应与胞外Ca2+内流、CaM-PK以及PKC有关,并提示UⅡ可能在肾纤维化发生和发展过程中发挥着重要作用。更多还原

【Abstract】 Objective:To investigate the proliferation effect of urotensin Ⅱ(UⅡ)on glomerular mesangial cells(GMC)of rats,and to study the signal transduction pathways.Methods:GMC proliferation was examined by the increase in 3H-thymidine(3H-TdR)incorporation into DNA.Different inhibitors were used to study the signal transduction pathways involved in the effect of UⅡ.Results:UⅡ[(10-9～10-7)mol/L]induced 3H-TdR incorporation in a concentration-dependent manner,which was increased by 86.9%,105.8% and 134.2%(P<0.01)in 10-9,10-8 and 10-7 mol/L groups,respectively,compared with the control group.The Ca2+ channel blocker nicardipine(105mol/L),protein kinase C(PKC)inhibitor H7(10-5mol/L)and CaM-PK inhibitor W7(10-5mol/L)significantly inhibited the effect of UⅡ,which was decreased by 42.3%、49.3%和34.1%(P<0.01), compared with the UⅡ group(10-8mol/L).Howe-ver,PD98059(10-5mol/L),an inhibitor of mitogen-activated protein kinase, couldn’t inhibit the effect.Conclusion:UⅡ can stimulate GMC proliferation,through Ca2+,PKC and CaM-PK signal transduction pathways, and may play important roles in the development of renal fibrosis.更多还原