钙信号在尾加压素-Ⅱ促血管平滑肌增殖中的作用  

Role of calcium signal in proliferation of vascular smooth muscle cells induced by urotensin Ⅱ

作　　者：张正浩[1] 张孙曦[1] 李菊香[2] 何其华[1] 牛大地[2] 王述姮[2] 袁杰[2] 唐朝枢[2] 

机构地区：[1]北京大学基础医学院生物物理学系,北京100083 [2]北京大学基础医学院生理学系,北京100083

出　　处：《北京大学学报（医学版）》2002年第3期261-265,共5页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金 (3 973 0 2 2 0 )资助~~

摘　　要：目的 :探讨钙信号在尾加压素 Ⅱ (urotensin Ⅱ ,UⅡ )促血管平滑肌细胞 (vascularsmoothmusclecell,VSMC)增殖中的作用。方法 :在离体培养的VSMC上 ,用流式细胞仪和3 H TdR参入的方法探讨UⅡ的促增殖效应 ;在离体孵育的大鼠主动脉平滑肌组织上观察UⅡ对平滑肌45Ca2 + 摄入的影响 ;应用激光共聚焦显微镜检测UⅡ作用后细胞内游离钙的改变。结果 :UⅡ (10 -9～ 10 -7mol·L-1)浓度依赖地刺激VSMC的DNA合成 ,并诱导细胞由静止向增殖状态转化。与对照组相比 10 -8mol·L-1UⅡ使细胞的增殖指数 [(G2 M +S) % ]增加 192 % (P <0 .0 1)。钙通道阻断剂尼卡地平和Ca2 + 螯合剂EDTA均可阻断UⅡ对VSMC的促增殖效应 ,其中UⅡ (10 -8mol·L-1)与尼卡地平 (10 -5mol·L-1)共同孵育的VSMCDNA合成量仅为单纯UⅡ (10 -8mol·L-1)组的 5 9.0 %。UⅡ (10 -10 ～ 10 -8mol·L-1)可浓度依赖地使胸主动脉对45Ca2 + 的摄入增加 ,尼卡地平 (10 -5mol·L-1)也可显著对抗UⅡ (10 -8mol·L-1)对45Ca2 + 摄入的诱导作用 (P值均小于 0 .0 1)。用激光共聚焦显微镜观察发现UⅡ作用后细胞内Ca2 + 浓度迅速升高 ,持续约 3min ,形成钙波。结论 :UⅡ可通过促进细胞Ca2 + 摄取和增加细胞内Ca2 + 浓度 。SUMMARY Objective: To investigate the role of calcium signal in the proliferation of vascular smooth muscle cells (VSMC) induced by Urotensin Ⅱ (UⅡ). Methods: The effect of UⅡ on the proliferation of VSMC was measured by 3H TdR incorporation and Flowcytometry method. The action of UⅡ on the 45 Ca 2+ uptake of rat aorta medium membrane was estimated in vitro . Technique of Laser Scanning Confocal Microscope (LSCM) was used to monitor the change of Ca 2+ in the cytoplasm induced by UⅡ.Results: UⅡ (10 -9 ～10 -7 mol·L -1 ) increased the DNA synthesis of VSMC and promoted the transformation of the cells from resting state to a proliferative one in a concentration dependent manner. UⅡ (10 -8 mol·L -1 ) increased the Proliferation Index [PI= (G 2 M+S)%] by 192% as compared with the control. Nicardipine, a calcium channel blocker, and EDTA, a calcium chelate agent, both significantly inhibited the UⅡ induced proliferation of VSMC. After incubation of VSMC with both nicardipine(10 -5 mol·L -1 ) and UⅡ(10 -8 mol·L -1 ), the DNA synthesis in VSMC was only 59.0% of that in the UⅡ(10 -8 mol·L -1 ) alone group. UⅡ stimulated 45 Ca 2+ uptake of aorta was increased in a concentration dependent manner, which was significantly inhibited by pretreatment with nicardipine. UⅡ produced a rapid increase in cytoplasmic Ca 2+ concentration and the Ca 2+ wave persisted about 3 min. Conclusion: UⅡ promotes the proliferation of VSMC through stimulating the Ca 2+ uptake from extracellular calcium and increasing cytoplasmic Ca 2+ concentration

关 键 词：钙信号 尾加压素-Ⅱ 血管平滑肌增殖 信号传递 药理学 

分 类 号：R973[医药卫生—药品]