摘要
目的:研究细胞外信号调节激酶(extracellularsignal-regulatedkinase,ERKs)信号途径在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)介导的大鼠血管平滑肌细胞(vascularsmoothmusclecell,VSMC)促增殖等反应中的作用及其可能的调控机制。方法:选用6周龄230g清洁级SD大鼠2只:本实验在长海医院中心实验室完成。实验依随机数字表分为正常对照组、AngⅡ诱导组、PD098059预处理组、U0126预处理组。每组均为3孔(n=3)。实验以通过3H-胸苷(3H-TdR)掺入率与3H-亮氨酸掺入率分别反映VSMC的DNA代谢与蛋白质合成代谢速率;并通过给予MAPK激酶特异性抑制剂PD098059及ERKs抑制剂UO126预处理,观察它们对细胞蛋白合成和DNA代谢及细胞增殖的影响。结果:①AngⅡ(1×10-7mmol/L)处理30minVSMC3H-胸苷掺入率和3H-亮氨酸掺入率均明显增高(增加207.2%,P<0.01);②AngⅡ增高3H-胸苷掺入的作用可明显被PD098059所抑制(增高抑制率52.3%,P<0.01)和完全被UO126所抑制(增高抑制率91.7%,P<0.01);③AngⅡ增高3H-亮氨酸掺入的作用可部分被PD098059所抑制(增加抑制率29.3%,P<0.05)和明显被UO126所抑制(增加抑制率64.6%,P<0.01)。结论:ERKs激活在血管紧张素Ⅱ导致VSMC增殖反应中具有重要作用,并可通过ERKs信号途径的特异性抑制剂的抑制效应,影响血管平?
AIM:To study the effect of extracellular signal regulated kinase(ERKs) on angiotensin Ⅱ(AngⅡ) induced proliferation of rat vascular smooth muscle cells (VSMC) and its possible regulating mechanism.METHODS: Two 6 month SD rats,weighing 230 g,clear grade,were selected.This experiment was carried out in the Central Laboratory of Changhai Hospital.With the method of random figure,there were four groups:normal control group,Ang Ⅱinduced group,PD098059 pretreated group and U0126 pretreated group.Three holes were in each group (n=3).Velocity of DNA metabolism and protein anabolism of VSMC were reflected by incorporation rate of thymidine ( TdR) and leucine; and the effect on cellular protein synthesis and DNA metabolism and cellproliferation was observed by MAPK kinase specific inhibitor PD098059 and ERKs inhibitor UO126 pretreatment.RESULTS: ①Incorporation rate of TdR and leucine were both significantly increased after treated with AngⅡ(1×10-7mmol/L) for 30 minutes (increased 207.2%, P< 0.01); ②Increasing effect of AngⅡon TdR could be significantly inhibited by PD098059(growing inhibitory rate was 52.3%, P< 0.01) and completely inhibited by UO126 (growing inhibitory rate was 91.7%, P< 0.01); ③Increasing effect of AngⅡon leucine was partially inhibited by PD098059 (growing inhibitory rate was 29.3%, P< 0.05) and significantly inhibited by U0126(growing inhibitory rate was 64.6%, P< 0.01). CONCLUSION: ERKs activation plays an important role in AngⅡinduced VSMC proliferation, and can influence the proliferation of VSMC by ERKs signal regulated specific inhibitor.
出处
《中国临床康复》
CSCD
2004年第30期6614-6615,共2页
Chinese Journal of Clinical Rehabilitation
