尾加压素Ⅱ促进肾系膜细胞增殖的细胞内机制研究_医学论文.docVIP

尾加压素Ⅱ促进肾系膜细胞增殖的细胞内机制研究_医学论文 尾加压素Ⅱ促进肾系膜细胞增殖的细胞内机制研究_医学论文 【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GMC　3H_TdR掺入，分别较对照组高86.9%、105.8%和134.2%(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%(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(Pgt0.05)。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。 【关键词】 肾系膜细胞 增殖 尾加压素 信号转导 　　Mechanisms of Proliferation Effect of Urotensin Ⅱ on Glomerular Mesangial Cells of Rats 　　ZHANG Yong_gang，WEI Rui_hong，LI Yu_guang，PANG Yong_zheng，TANG Chao_shu 　　(Department of Cardiovascular Diseases, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China；Department of internal medicine, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China；Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China) 　　［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%(0.01)in 10-9, 10-8 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(10-5mol/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%(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