阿托伐他汀对大鼠血清VEGF、Ang-1以及Ang-2影响

Atorvastatin on the plasma of VEGF,Angiopoietin-1 and Angiopoietin-2 in rats

目的通过研究阿托伐他汀对健康大鼠血清血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)以及血管生成素-2(Ang-2)水平影响的时间、剂量依赖性,探讨阿托伐他汀作为血管病预防用药在非病理情况下对血管新生的影响。方法将30只健康SD大鼠随机分成对照组、低剂量组与高剂量组,每组各10只,分别连续灌胃生理盐水、低剂量和高剂量的阿托伐他汀28 d。于第1天给药前、第7天给药后24 h、第28天给药后24 h采静脉血,分离血清,用酶联免疫吸附法(ELISA)检测血清VEGF、Ang-1以及Ang-2。结果第7天,高剂量组血清VEGF、Ang-2的变化明显升高[(347.20±28.00)pg/ml,(1 915.00±543.30)ng/L,P<0.05];低剂量组血清VEGF、Ang-1的变化明显升高[(653.60±57.10)pg/ml,(1 718.00±283.00)pg/ml,P<0.05],Ang-2的变化明显降低[(-3 016.00±483.00)ng/L,P<0.05];对照组无明显变化。第28天各组血清VEGF、Ang-1、Ang-2水平无明显变化。结论健康大鼠短期应用阿托伐他汀明显改变血清血管特异性生长因子水平,且应用剂量不同变化效果不同。

Objective To investigate the time and dose dependence of the effects of atorvastatin on plasma of vascular endothelial growth factor（ VEGF）, Angiopoietin-1 （ Ang-1 ） and Angiopoietin-2 （ Ang-2 ） in normal rats, so as to explore the effect of atorvastatin on angiogenesis in non-pathological conditions. Methods A total of 30 healthy SD rats were randomly divided into the control group, the low-dose group and the high-dose group, with 10 rats in each group. Rats in the three groups were feeded with saline, low-dose and high-dose atorvastatin ,respectively for 28 days. Venous blood samples were taken on day 1,24 hours after day 7 and 24 hours after day 28. Serum VEGF,Ang-1 and Ang-2 were measured by ELISA after serum separation. Results On day 7,the levels of plasma VEGF and Ang-2 in the high-dose group increased significantly [ （ 347.20±28. 00 ） pg/ml, （ 1 915.00±43.30 ） ng/L, P 〈 0. 05 ], the levels of plasma VEGF and Ang-1 in the low-dose group increased significantly[ （653.60±57. 10）pg/ml, （1 718.00±283.00 ）ng/L, P 〈0. 05 ] , the level of plasma Ang-2 reduced significantly [ （-3 016. 00±483.00 ）ng/L, P 〈 0. 05 ] , there was no significant change in the control group;on the day 28 ,the levels of plasma VEGF, Ang-1 and Ang-2 of each group did not have any significant change. Conclu- sion Short-time atorvastatin administration could significantly change the levels of plasma VEGF, Ang-1 and Ang-2 in normal rats, and the different effects dependent on the variation dose of atorvastatin.