血管紧张素Ⅱ对血管平滑肌血小板源生长因子rn受体β亚单位的调节

摘要

AIM: To investigate the crosstalk between angiotensin Ⅱ (AngⅡ)-mediated and platelet-derived growth factor (PDGF)-mediated signal transduction in vascular smooth muscle proliferation.METHODS: A model of renal hypertension was made by two kidney/one-clip operation. Level of PDGF receptor β subunit of aorta was measured by Western Blot analysis. The effect of Ang Ⅱ on PDGF receptor β subunit expression was investigated in culture rat aortic vascular smooth muscle cells (VSMC).RESULTS: Systolic blood pressure obviously increased at 8th week after operation, whereas the level of PDGF receptor β subunit of aorta significantly increased by 126.6% (P＜0.05) in 2K1C rats compared with control group. The expression of PDGF receptor β subunit in cultured VSMC stimulated by AngⅡ was higher than that of control by 192.74%(P＜0.01). The effect of AngⅡ was inhibited remarkably by pretreated with losartan, a kind of specific AngⅡ receptor 1 (AT1) subtype antagonist and U73122, a kind of phospholipase C inhibitor. The effect was partly blocked by PD98059, which inhibit the activity of mitogen-activated, ERK-activating kinase (MEK).CONCLUSION: AngⅡ-induced PDGF receptor β subunit expression is regulated by the AT1 and its downstream signal molecule-PLC and ERK, might participate in the intracellular signal transduction pathway.%目的：观察血管紧张素Ⅱ对血管平滑肌血小板源生长因子(PDGF)受体β亚单位的调节，探讨两条信号转导途径的交互作用在血管平滑肌细胞(VSMC)增殖中的意义。方法：制备两肾一夹肾性高血压大鼠模型，免疫印迹法检测主动脉组织PDGF受体β亚单位的含量。培养大鼠主动脉VSMC，观察血管紧张素Ⅱ(AngⅡ)对PDGF受体β亚单位的影响。结果：两肾一夹大鼠术后8周动脉血压明显增高，同时主动脉PDGF受体β亚单位的表达高于对照组126.6%(P＜0.05)。AngⅡ刺激培养的VSMC可导致PDGF受体β亚单位上调192.74%(P＜0.01），该效应可被Ⅰ型AngⅡ受体(AT1)的拮抗剂losartan和磷脂酶C(phospholipase c, PLC)的抑制剂U73122完全阻断(P＜0.01)，但仅被丝裂原活化蛋白激酶激酶抑制剂PD98059部分阻断(P＜0.01)。结论： AngⅡ可以通过AT1及下游的信号分子PLC上调PDGF受体β亚单位的表达，而细胞外信号调节激酶可能参与AngⅡ的胞内信号转导。