阿伐他汀对成年大鼠心肌成纤维细胞分泌内皮素-1及一氧化氮合酶/一氧化氮系统活性的影响

Effect of atorvastatin on the ET-1 and NOS-NO system activity in adult rat cardiac fibroblasts

目的 :探讨阿伐他汀 (Atorvastatin)对大鼠心肌成纤维细胞 (CFs)分泌内皮素 1(ET 1)含量及一氧化氮合酶 /一氧化氮 (NOS NO)系统活性的影响。 方法 :采用胰蛋白酶和胶原酶混合消化法 ,差速贴壁获取CFs。应用放免法、硝酸还原酶法和分光光度法分别测定不同干预条件下CFs培养液中ET 1水平及NOS NO活性。 结果 :①阿伐他汀呈浓度依赖性抑制CFs分泌ET 1,10 -6、10 -5和 10 -4mol/L阿伐他汀组与对照组相比差异非常显著 (均P <0 .0 1) ;10 -5和 10 -4mol/L阿伐他汀组分别与 10 -7和 10 -6mol/L阿伐他汀组相比差异非常显著 (均P <0 .0 1)。②阿伐他汀可升高CFsNO含量 ,10 -5和 10 -4mol/L阿伐他汀组与对照组相比差异显著 (P <0 .0 5 )和非常显著 (P <0 .0 1) ;10 -4mol/L阿伐他汀组与 10 -7mol/L阿伐他汀组相比差异显著 (P <0 .0 5 )。③阿伐他汀可增强CFsNOS活性 ,10 -5和 10 -4mol/L组阿伐他汀与对照组相比差异显著 (P <0 .0 5 )或非常显著 (P <0 .0 1) ;10 -4mol/L与 10 -7mol/L阿伐他汀组相比差异显著 (P <0 .0 5 )。 结论 :阿伐他汀能抑制CFs分泌ET 1,提高CFsNOS NO系统活性 ,拮抗血管紧张素Ⅱ (AngⅡ )的部分生物活性 ,发挥其逆转心室重塑。

Objectives: To investigate the effects of Atorvastatin on the secretion of ET 1 and NOS NO activity from adult rat cardiac fibroblasts (CFs). Methods: Isolated and cultured CFs of adult Sprague Dawley (SD) rats were used as experiment model. The change of Endothelin 1 (ET 1) was measured by radioimmunoassay. Nitric oxide (NO) content and nitric oxide synthase (NOS) activity were measured by spectrophotometry. Results: ① The secretion of ET 1 from CFs decreased graduately with the elevation of Atorvastatin concentrations.The content of ET 1 in 10 -7 mol/L, 10 -6 mol/L, 10 -5 mol/L and 10 -4 mol/L Atorvastatin groups were significantly lower than that of control group (all P < 0.01) . ② The content of NO in 10 -5 mol/L and 10 -4 mol/L Atorvastatin groups were significantly higher than that of control group(all P <0.05). ③ There was very significant increase of NOS activity in 10 -5 mol/L and 10 -4 mol/L Atorvastatin groups, compared with control group(all P <0.05). Conclusions:Atorvastatin have inhibitory effects on the secretion of ET 1 and increase the NOS NO activity in cultured adult rat CFs.