坎地沙坦,PD123319及金雀异黄素对大鼠血管平滑肌细胞迁移影响

目的:探讨血管紧张肽Ⅱ(AngⅡ)不同受体亚型(AT1,AT2)在血管平滑肌细胞(VSMC)迁移中的作用。方法:以体外培养VSMC为基础,采用改良Boyden小室,对不同浓度AT1拮抗剂坎地沙坦(CV)、AT2拮抗剂PD123319(PD)和酪氨酸激酶(PTKs)抑制剂金雀异黄素作用下AngII诱导产生的VSMC跨膜迁移细胞数进行评价。分对照组、AngII组、AngII+10-10～10-5mol·L-1CV组、AngⅡ+10-9～10-6mol·L-1PD组、AngⅡ+CV+PD组、AngⅡ+金雀异黄素组。结果:与对照组相比,AngⅡ组跨膜迁移细胞数明显增加,P<0.01。坎地沙坦在10-10～10-5mol·L-1的浓度范围内,呈剂量依赖性抑制由AngⅡ介导的VSMC迁移(r=0.95,P<0.05)。PD123319对此无明显的增强或抑制作用。金雀异黄素组VSMC跨膜迁移细胞数低于AngⅡ组,高于对照组。结论:AngⅡ影响VSMC迁移能力的生物学效应由AT1介导;AT2在VSMC迁移过程中不起作用或者不起主要作用。酪氨酸激酶的激活也参与了AngⅡ诱导的VSMC迁移的信号转导过程。

Effect of candesartan,PD123319 and genistein on migration of vascular smooth muscle cells in rats

AIM: To determine the biotic effect of angiotensin II(AngⅡ) receptors subtypes(AT1, AT2) on AngⅡ induced migration of rat vascular smooth muscle cells (VSMC). METHODS: VSMC isolated from aortic media of Wistar rats were cultured by the modified explanted method. Migration of rat VSMC was assayed by a modification of Boyden's chamber method in presence of different concentrations of AT1 antagonist candesartan(CV), and AT2 antagonist PD123319 (PD) respectively. The migration assays were performed also in presence of genistein, a specific tyrosine kinase (PTKs) inhibitor. Groups in this experiment included control group, Ang Ⅱ group, AngⅡ+10 -10-10 -5 mol·L -1 CV group, AngⅡ+10 -9-10 -6 mol·L -1 PD group, AngⅡ+CV+PD group and AngⅡ+genistein group. RESULTS: The migration of VSMC was significantly increased by adding 10 -7 mol·L -1 Ang Ⅱ (P<0.01 vs control). AngⅡ induced migration of VSMC was inhibited significantly by CV (10 -10-10 -7 mol·L -1) in a concentration-dependent manner(r=0.95, P<0.05). AT2 antagonist PD123319 showed no significant inhibitory or enhanced effect (P<0.01). The migration of VSMC in genistein group was lower than Ang Ⅱ group, but was higher than control group. CONCLUSION: The effect of AngⅡ on rat VSMC migration is mediated by AT1, while AT2 has no significant effect. The activation of PTKs also involves in the Ang Ⅱ induced transduction of VSMC migration.