辛伐他汀联合缬沙坦改善肾衰竭大鼠血管钙化的实验研究

Experimental Study of Simvastatin Combined with Valsartanfor Improving in Vascular Calcification of Rats with Renal Failure

目的:探究辛伐他汀联合缬沙坦对肾衰竭大鼠血管钙化的影响及其潜在的分子机制。方法:随机选取10只大鼠作为正常对照组,其余大鼠用含0. 75%腺嘌呤的饲料饲喂6周诱导肾衰竭,随机选取10只作为肾衰竭组,其余大鼠再用高钙饲料饲喂2周,建立肾衰竭大鼠血管钙化模型,并随机分成4组:肾衰竭血管钙化组、辛伐他汀组(2 mg·kg^(-1))、缬沙坦组(1 mg·kg^(-1))和联合治疗组(2 mg·kg^(-1)的辛伐他汀和1 mg·kg^(-1)的缬沙坦)。均行灌胃治疗,正常对照组、肾衰竭组和肾衰竭血管钙化组分别给予等量容积的生理盐水灌胃治疗,治疗2周,采用全自动生化分析仪检测大鼠血清中钙(Ca)含量,von Kossa染色和主动脉烤干法检测动脉血管Ca含量,实时荧光定量PCR和蛋白免疫印迹检测核结合因子α1(cbfα1)表达情况。结果:肾衰竭血管钙化模型组血清中Ca的浓度、动脉血管中的Ca含量以及cbfα1表达水平显著高于正常对照组(P <0. 05);各给药组动脉血清中Ca的浓度、动脉血管中的Ca含量以及cbfα1表达水平显著低于肾衰竭血管钙化组(P <0. 05);联合治疗组血清中Ca的浓度、动脉血管中的Ca含量以及cbfα1表达水平显著低于辛伐他汀组和缬沙坦组(P <0. 05)。结论:辛伐他汀联合缬沙坦能够改善肾衰竭大鼠血管钙化,推测这一作用是通过下调cbfα1表达水平实现的,为肾衰竭血管钙化的治疗提供一定理论依据。

Objective: To explore the influence of simvastatin combined with valsartan on the vascular calcification in rats with renal failure and the potential molecular mechanisms. Methods: Totally 10 rats were selected randomly as the normal control group,and the other rats were fed with diet containing 0. 75% adenine to induce renal failure. Totally 10 rats with renal failure were randomly selected as the renal failure group,and the other rats with renal failure were fed with high calcium diet for two weeks,and the vascular calcification model was established in rats with renal failure. The renal failure rats with vascular calcification were divided into four groups,renal failure vascular calcification group,simvastatin group(2 mg·kg-1),valsartan(1 mg·kg-1) group and the combination treatment group(2 mg·kg-1 simvastatin + 1 mg·kg-1 valsartan). All the rats were with gavage administration. The normal control group,renal failure group and renal failure vascular calcification group were given normal saline at the same volume. The treatment course was 2 weeks. The content of Ca in venous blood of rats was detected by an automatic biochemical analyzer,and vascular Ca content was detected by von Kossa staining and aortic baking method. Real-time fluorescent quantitative PCR and Western blot were used to detect the cbfα1 expression. Results: The concentration of serum Ca,the content of Ca in arterial blood vessels and cbfα1 expression in renal failure vascular calcification model group were all significantly higher than those in the normal control group( P <0. 05). The concentration of Ca in arterial serum,the content of Ca in arterial blood and cbfα1 expression level in the treatment group were significantly lower than those in renal failure vessel calcification group( P < 0. 05). The concentration of Ca,the content of Ca in arterial blood and cbfα1 expression level in the combination treatment group were significantly lower than those in simvastatin group and valsartan group( P < 0. 05). Conclusion: Simvastatin combined with valsartan can improve vascular calcification of rats with renal failure,which is related with the down-regulation of cbfα1 expression. The study provides theoretical basis for the treatment of renal failure vascular calcification.