尾加压素Ⅱ对血管平滑肌细胞增殖的影响  

Stimulating proliferation of aorta smooth muscle cells of rat by rat urotensin Ⅱ

作　　者：张勇刚[1] 齐永芬[1] 夏春芳[1] 庞永正[1] 杨军[1] 张肇康[1] 唐朝枢[1] 

机构地区：[1]北京大学第一医院心血管病研究所,北京100034

出　　处：《中国药理学通报》2001年第2期155-157,共3页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题;No 39730220

摘　　要：目的研究体内新发现的缩血管活性肽尾加压素Ⅱ（ｕｒｏｔｅｎｓｉｎ Ⅱ， Ｕ Ⅱ）对大鼠主动脉平滑肌细胞增殖作用的影响以及ＵⅡ作用的细胞内信号转导机制。方法在培养的大鼠主动脉平滑肌细胞（ＡＳＭＣ）上，采用［３Ｈ］－胸腺嘧啶（［３Ｈ］－ＴｄＲ）参入法，观察 ＵⅡ对细胞 ＤＮＡ合成的刺激作用；加入不同的细胞内信号转导阻断剂，观察对ＵⅡ效应的影响。结果 Ｉ× １０－９～ １× １０－７ ｍｏｌ·Ｌ－１ ＵⅡ以浓度依赖方式促进 ＡＳＭＣ［３Ｈ］－ＴｄＲ参入增加， １× １０－９、１× １０－８和 １×１０－７ｍｏｌ·Ｌ－１ＵⅡ组［３Ｈ］－ＴｄＲ参入量分别较对照组增加２２％（Ｐ＜０．０５），５７％（Ｐ＜０，０１）和６５％（Ｐ＜０．０１）。ＵⅡ的效应能被钙通道阻断剂尼卡地平、ＰＫＣ阻断剂Ｈ７、钙调素激酶（ＣａＭ－ＰＫ）阻断剂 Ｗ７和 ＭＡＰＫ阻断剂 ＰＤ９８０５９所阻断，抑制率分别为５５％（Ｐ＜０．０１），２７％（Ｐ＜０．０１），１８％（Ｐ＜０．０５）和１６％（Ｐ＜０．０５）。结论 ＵⅡ是一种新发现的强烈的促ＡＳＭＣ增生的内源性丝裂原，其促丝裂效应可能通过Ｃａ２＋、ＰＫＣ、ＣａＭ－ＰＫ和ＭＡＰＫ来介导。AIM To investigate effect of urotensin Ⅱ (U Ⅱ )on proliferation of aorta smooth muscle cells (ASMC) of rat and study the signal transduction pathway of it. MEfHODS in cultured ASMC of rat, U Ⅱ was used to stimulate proliferation of these cells and levels of [3H]-TdR incorporation were used to evaluate the sped of DNA synthesis, and different inhibitors were ed to study the action of different signal transduction pathway of mitogenic effect of UⅡ on VSMC. RESULTS. 1 × 10-9~l × 10-7 mol. L-l U Ⅱ caused marked concentration-de pendent increasing of [3H]-TdR incorporation of ASMC [3H]-TdR incorporation of 1 × 10-9, 1 × 10-8 and １ × 10-7 mol. L－l U Ⅱ were 22%'(P < 0.05), 57% (P< 0.01)and 65% (P < 0.01)higher than control. Nicardipine, H7, W7 and PD98059, which are inhibitors of chum channel, PKC, PK and MAPK respectively, inhibited the effects of U Ⅱ obviously, with the inhibitory rate by 55 % (P< 0.01), 27% (P< 0.01 ), 18% (P < 0.05)and 16% (P<0.05)respectively. CONCLUSION U Ⅱ is a strong mitogen for VSMC and the mitogenic effect of U Ⅱ is probably mediated by Ca2+, PKC, CaM-PK and MAPK signal transduction pathway.

关 键 词：尾加压素Ⅱ 细胞增生 有丝分裂原 血管平滑肌细胞 

分 类 号：R972[医药卫生—药品] R543[医药卫生—药学]