洛沙坦抑制平滑肌细胞增殖和神经肽Y作用的关系

The Inhibiting Effects of Losartan on Proliferation of Cultured Arterial Smooth Muscle Cell and Its Relationship with Neuropeptide Y

【目的】探讨洛沙坦 (Losartan)对高血压病人血管重塑的作用机制以及肾素 血管紧张素系统和神经肽Y(NPY)在高血压、动脉粥样硬化等心血管疾病发生的作用。【方法】实验分为对照组、Losartan组、NPY组及Losartan +NPY 4组 ,应用生物化学方法 (MTT)和荧光免疫组化定量技术 (ACAS 5 70共聚焦激光扫描显微细胞仪 ) ,每组扫描细胞总数在 2 0 0个以上 ,观察Losartan对体外培养血管平滑肌细胞 (VSMC)增殖的影响和与NPY作用的关系。【结果】对照组、Losartan组、NPY组及Losartan +NPY 4组VSMC增殖活度 (吸光度表示 )分别为 0 2 2 39± 0 0 0 10、0 2 0 45± 0 0 0 13、0 2 6 2 6± 0 0 0 2 5、0 2 44 0± 0 0 0 13,增殖细胞核抗原 (PCNA)荧光值分别为 15 43± 2 0 0、1339± 2 33、16 49± 2 33、15 45± 2 5 6。Losartan可抑制体外培养和NPY作用下VSMC的增殖 ,与对照组相比 ,VSMC增殖活度和PCNA的表达均明显降低 (P <0 .0 1)。【结论】Losartan对高血压的治疗既有Losartan对VSMC增殖的抑制作用 ,也有对NPY等缩血管因素的拮抗作用。

Objective To explore the mechanism of action of Losartan on vascular remodelling in hypertension and its relationship with neuroendocrine factor and renin-angiotensin system. Methods The study consisted of control group and other three treatment groups: Losartan group、NPY group、and Losartan+NPY group. More than 200 cells were scanned in each group. The methods of cellular culture, biochemistry and quantitative immunocytochemistry through ACAS570 were applied to investigate the proliferation of vascular smooth muscle cell (VSMC) and the expression of proliferating cell nuclear antigen (PCNA) in cultured rat VSMC treated with Losartan and Neuropeptide Y (NPY) stimulation. Results VSMC proliferation (by absorbauce) in the control group and other three examed groups: Losartan group、NPY group and Losartan+NPY group were 0.223 9±0.001 0、0.204 5±0.001 3、0.262 6±0.002 5、0.244 0±0.001 3, and PCNA (by fluorescence intensity) were 1 543±200、1 339±233、1 649±233、1 545±256. It was observed that losartan could inhibit the VSMC proliferation in vitro culture with and without NPY simulation. Compared with the control groups, the VSMC proliferation activity and expression of PCNA were obviously descreased in the losartan treated groups. Conclusion The results demonstrate that losartan has the inhibitive effects on VSMC profiferation and PCNA expression. The results also suggest that losartan has anti-NPY effect on VSMC in vascular remodelling of hypertensive vessels.