联合应用氨氯地平与阿托伐他汀改善自发性高血压大鼠动脉弹性功能及主动脉重构

Combination of Amlodipine and Atorvastatin Improved Aortic Elasticity and Remodeling in Spontaneously Hypertensive Rats

目的探讨氨氯地平与阿托伐他汀联合应用对自发高血压大鼠(SHR)动脉弹性功能及主动脉重构的影响。方法雄性SHR 40只随机分为空白对照组(n=10)、氨氯地平组[n=10,氨氯地平10 mg/(kg.d)]、阿托伐他汀组[阿托伐他汀10 mg/(kg.d),n=10]、氨氯地平与阿托伐他汀联合用药组[氨氯地平10 mg/(kg.d),阿托伐他汀10 mg/(kg.d),n=10]。对各组灌胃12周,对照组以等量的蒸馏水灌胃。12周后检测主动脉脉搏波传导速度(PWV)与增强指数(AI),光镜下测量主动脉中膜厚度、血管内径及中膜厚度与内径比值(MT/LR),Masson三色染色分析胶原纤维含量,碱解法测定羟脯氨酸含量。结果治疗12周后,SHR各组血脂水平差异无统计学意义。氨氯地平与联合用药均可使血压显著下降,但两组间血压差异无统计学意义。氨氯地平、阿托伐他汀及联合用药均可显著降低主动脉AI、中膜厚度、MT/LR及胶原纤维含量;其中氨氯地平及联合用药均显著降低PWV。与氨氯地平单独使用相比,联合用药可使AI、中膜厚度、MT/LR、胶原纤维含量进一步降低。结论联合应用氨氯地平与阿托伐他汀可较单用氨氯地平进一步改善高血压大鼠主动脉弹性,其主要机制可能与降低主动脉胶原纤维含量、改善主动脉重构有关,且这种有益作用是不依赖阿托伐他汀的降脂作用的。

Objective To investigate the effects of combined administration of amlodipine and atorvastatin on aortic elasticity and remodeling in spontaneously hypertensive rats（SHR）. Methods Forty male SHR were randomly allocated into vehicle group （n= 10）, amlodipine-treated group [n = 10, amlodipine 10 mg/（ kg·d）], atorvastatin-treated group [n = 10, atorvastatin 10 mg/（ kg · d）], and combination group [n = 10, atorvastatin 10 mg/（kg · d） and amlodipine 10 mg/（kg· d）] for 12 weeks. Arterial pulse wave velocity （PWV） , aortic augmentation index （AI） , aortic media thickness （MT） , luminal radius （LR）, and the ratio of MT/LR were measured after 12-week treatment. The content of collagen of aortic segment was evaluated by Masson trichrome staining. The content of hydroxyproline was measured by alkaline hydrolysis. Results After treatment, there were no significant differences among lipid levels in each SHR groups. Although the blood pressure in amlodipine-treated group and combination group was decreased to a greater extent, no significant difference of blood pressure between them. Both amlodipine, atorvastatin and combination treatment significantly decreased aortic AI, aortic MT, MT/ LR and contents of collagen were significantly decreased. Compared with amlodipine monotherapy, the aortic AI, MT, MT/LR, and contents of collagen were decreased to greater extent in the combination group. Conclusion Combined amlodipine and atorvastatin improves the elastic properties of the aorta, associated with the decrease in aortic collagen content and amelioration of aortic remodeling. These beneficial effects seem to be independent of lipid lowering effect of atorvastatin.