辛伐他汀对血管紧张素Ⅱr刺激的肾上腺皮质癌H295R细胞的分泌和增殖的影响

摘要

目的 研究辛伐他汀对血管紧张素Ⅱ(AngⅡ)刺激的肾上腺皮质癌H295 R细胞的分泌和增殖的影响.方法 H295R细胞分为对照组、AngⅡ(100 nmol/L)处理组、辛伐他汀(10μmol/L)处理组和AngⅡ+辛伐他汀处理组,用化学发光法检测培养液中的皮质醇;用放射免疫分析法(RIA)检测培养液中的醛固酮;用实时荧光定量PCR检测11β-羟化酶(CYP11B1)和醛固酮合成酶(CYP11B2)的mRNA表达;用MTS法观察细胞增殖.结果 与对照组相比,AngⅡ刺激皮质醇和醛固酮分泌及其合成酶CYP11B1与CYP11B2 mRNA的表达,辛伐他汀抑制皮质醇分泌及其合成酶CYP11B1 mRNA的表达(P<0.05);与单独AngⅡ处理组相比,AngⅡ+辛伐他汀组能显著抑制AngⅡ刺激的皮质醇和醛固酮分泌及其合成酶CYP11 B1与CYP11 B2 mRNA的表达(P<0.05);AngⅡ对H295 R细胞增殖无明显影响,辛伐他汀抑制细胞增殖,并且,辛伐他汀与AngⅡ联合处理细胞,这种抑制作用更显著(P<0.05).结论 辛伐他汀抑制AngⅡ诱导的肾上腺皮质癌H295R细胞的皮质醇与醛固酮的分泌;辛伐他汀抑制H295R细胞增殖,与AngⅡ联合处理细胞这种抑制作用更显著.%Objective To investigate the potential effects of simvastatin on angiotensin Ⅱ-stimulated secretion and proliferation of adrenocortical carcinoma H295R cells.Methods The H295R cells were divided into control group, Angiotensin Ⅱgroup, simvastatin group and Angiotensin Ⅱ plus simvastatin group.Cortisol in medium was determined by chemiluminescent method , and aldosterone was determined by radioimmunoassay .The mRNA expression of 11 beta-hydroxylase ( CYP11B1 ) and aldosterone synthase ( CYP11B2 ) were examined by RT-qPCR.Cell proliferation was detected by MTS method.Results Compared with control group, angiotensin Ⅱincreased the secretion of cortisol and aldosterone, and the expression of CYP11B1 and CYP11B2.Simvastatin decreased cortisol secretion and CYP11B1 mRNA expression ( P<0.05 ) .Simvastatin also inhibited angiotensinⅡ-induced the secretion of cortisol and aldosterone , and the expression of CYP 11 B1 and CYP11 B2 compared with Angiotensin Ⅱgroup ( P<0.05 ) .Angiotensin Ⅱhad no effect on cell proliferation , while simvastatin significantly inhibited cell proliferation .The inhibitory effect of simvastatin on proliferation was enhanced when simvastatin was prescribed with angiotensin Ⅱ( P<0.05 ) .Conclusions Simvastatin inhibits angiotensin Ⅱ-induced secretion of cortisol and aldosterone in H295R cells.Simvastatin inhibits cell proliferation, which could be enhanced by angio-tensin Ⅱ.