摘要
目的:研究丝裂原活化蛋白激酶(MAPK)信号途径在葡萄糖(GS)和/或血管紧张素Ⅱ(AngⅡ)介导大鼠动脉平滑肌细胞促增殖中的作用及其可能的调控机制.方法:实验以平滑肌细胞蛋白合成速率和蛋白含量为平滑肌细胞增殖的指标,以平滑肌细胞3H-亮氨酸掺入率表示细胞蛋白质合成速率,通过3H-胸苷(3H-TdR)反映平滑肌细胞DNA的代谢及细胞增殖情况;并通过给予PD098059及高浓度葡萄糖(HG)预处理,观察它们对细胞蛋白合成、DNA代谢及细胞增殖的影响.结果:①AngⅡ(10-7mol/L)处理平滑肌细胞,3H-胸苷掺入率明显增高;HG(25×10-3mol/L)处理平滑肌细胞,3H-胸苷掺入率明显增高;AngⅡ+HG处理平滑肌细胞3H-胸苷掺入率显著增高.②AngⅡ增加3H-胸苷掺入的作用可明显被PD098059所抑制;AngⅡ+HG增高3H-胸苷掺入的作用也可被PD098059所抑制.③AngⅡ(10-7mol/L)处理平滑肌细胞,3H-亮氨酸掺入率明显增高;HG(25×10-3mol/L)处理平滑肌细胞,3H-亮氨酸掺入率增加;AngⅡ+HG处理平滑肌细胞3H-亮氨酸掺入率显著增加.④AngⅡ增加3H-亮氨酸掺入的作用可部分被PD098059所抑制;AngⅡ+HG增加3H-亮氨酸掺入的作用可显著被PD098059所抑制.结论:应用MAPK的特异性抑制剂PD098059抑制血管平滑肌细胞的增殖,证明MAPK激活在GS和/或AngⅡ导致平滑肌细胞增殖反应中有重要作用.
AIM： To study the role of mitogen activated protein kinase（MAPK） in glucose （GS）/angiotensin Ⅱ （Ang Ⅱ ）- induced proliferation of rat vascular smooth muscle cell （VSMC）. METHODS： The protein sythesis rate and protein content were used as the indexes of VSMC proliferation in our study. The DNA synthesis rate was quantified by [ ^3H ] thymidine incorporation. The protein synthesis rate was quantified by [ ^3H ] leucine incorporation. Regulation of extracellular signal regulated kinase（ERKs） in Ang Ⅱ -induced proliferation were investigated by preincubation with either PD098059 or/and high glucose （HG）. RESULTS： Ang Ⅱ （ 10 -7 mmol/L） significantly increased [ ^3H ] thymidine incorporation and [^3H]leucine incorporation and HG （10^-3 mmol/L） significantly increased [^3 H ] thymidine incorporation and [^3 H ] leucine incorporation, and Ang Ⅱ ＋ HG exerted a more significant effect. Preincubation of VSMC with PD098059 significantly inhibited the increase of [^3 H ] thymidine incorporation induced by Ang lI and very significantly inhibited the increase of [^3H] thymidine incorporation induced by AngⅡ ＋ HG. Preincubation of VSMC with PD098059 partly inhibited the increase of [ ^3H ] leucine incorporation induced by Ang Ⅱ and significantly inhibited the increase of [ ^3H ] leucine incorporation induced by Ang Ⅱ ＋ HG. CONCLUSION ： The activation of MAPK plays an important role in VSMC growth and proliferation reaction induced by GS/Ang Ⅱ.
出处
《第四军医大学学报》
北大核心
2006年第22期2026-2028,共3页
Journal of the Fourth Military Medical University
