尾加压素Ⅱ促进肾系膜细胞增殖的细胞内机制研究  

Mechanisms of Proliferation Effect of Urotensin Ⅱ on Glomerular Mesangial Cells of Rats

作　　者：张勇刚[1] 魏睿宏[2] 李玉光[1] 庞永正[3] 唐朝枢[3] 

机构地区：[1]汕头大学医学院第一附属医院内科 [2]汕头大学医学院第二附属医院内科,广东汕头515041 [3]北京大学第一医院心血管病研究所,北京100034

出　　处：《汕头大学医学院学报》2007年第3期132-134,165,共4页Journal of Shantou University Medical College

基　　金：国家自然科学基金资助项目(30470730);中国博士后基金资助项目(2003033439)

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。Objective： To investigate the prolterafion 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 transdnction path- ways involved in the effect of UⅡ. Results： U Ⅱ [ （ 10^-9～10^-7） mol/L] induced 3 H-TdR incorporation in a concentrationdependent manner, which was increased by 86：9%, ,105.8% and 134.2%（P 〈0.01）in 10^-9, 10^-9 and 10^-7 mol/L groups, respectively, compared with the control group. The Ca2＋ channel blocker nicardipine（10^-5mol/L）, protein kinase C （PKC） inhibitor H7 （ 10^- 5 mol/L ） and CaM-PK inhibitor W7 （ 10- 5 mol/L ） significandy inhibited the effect of U Ⅱ, which was decreased by 42.3%, 49.3%和1 34.1%（P 〈 0.01）, compared with the UII group（10^-8mol/L）. However, PD98059（10^-5mol/L）, an inhibitor of mitogen-activated protein kinase, couldn＇t inhibit the effect. Conclusion： U II can stimulate GMC proliferation, through Ca^2＋ , PKC and CaM-PK signal transduction pathways, and may play important roles in the development of renal fibrosis.

关 键 词：肾系膜细胞 增殖 尾加压素Ⅱ 信号转导 

分 类 号：R364.31[医药卫生—病理学] R361.3[医药卫生—基础医学]