阿托伐他汀联合非诺贝特治疗混合性高脂血症的疗效及对肝功能的影响

Efficacy and Safety of Combination Therapy with Atorvastatin and Fenofibrate in Rats with Combined Hyperlipidemia

目的探讨阿托伐他汀与非诺贝特联合应用治疗混合性高脂血症的较佳给药剂量及方法,以及对肝功能和高敏C反应蛋白的影响。方法60只Wistar大鼠随机分为正常对照组、高脂对照组、阿托伐他汀组[1.8mg/(kg·d)]、顿服组[阿托伐他汀0.9mg/(kg·d)+非诺贝特18mg/(kg·d),顿服]及分服组[阿托伐他汀0.9mg/(kg·d)+非诺贝特18mg/(kg·d),早晚分开服用],实验过程共8周,复制高脂血症模型4周,用药4周。分别检测血脂、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和高敏C反应蛋白。结果8周末时,与高脂对照组比较,正常对照组及各用药组总胆固醇、低密度脂蛋白胆固醇及甘油三酯降低(P<0.01),与高脂对照组及阿托伐他汀组比较,联合用药组高密度脂蛋白胆固醇水平升高(P<0.01),甘油三酯水平降低(P<0.01)。8周末时,与正常对照组比较,高脂组及各用药组C反应蛋白水平升高(P<0.05);与阿托伐他汀组比较,高脂组C反应蛋白水平明显升高(P<0.01),联合用药组降低(P<0.05)。8周末时,与正常组比较,高脂组及各用药组丙氨酸氨基转移酶及天门冬氨酸氨基转移酶升高(P<0.01);与高脂组比较,各用药组丙氨酸氨基转移酶及天门冬氨酸氨基转移酶降低(P<0.05);与阿托伐他汀组和分服组比较,顿服组丙氨酸氨基转移酶及天门冬氨酸氨基转移酶水平升高(P<0.05)。结论阿托伐他汀与非诺贝特联合应用可增强调脂疗效及控制C反应蛋白的水平,较加倍剂量的阿托伐他汀效果更佳;二者联合应用时应适当减少各自剂量,早晚分开服用,在保护高脂血症对肝功能损害的同时减少药物性肝损害。

Aim To evaluate the efficacy and safty of combination therapy with atorvastatin and fenofibrate in rats with mixed hyperlipidemia. Methods 60 Wistar rots were randomized into normal group, control group, atorvastafin group, AFH group and AFF group. The groups were fed with high fatty foods, except Normal group fed with common foods. At the end of the fourth week, Atorvastatin group [ Atorvastafin 1.8 mg/（kg·d） ], AFH group [ Atorvastafin 0.9 mg/（kg·d） ＋ Fenofibrate 18 mg/（kg·d）, together], and AFF group [ Atorvastatin0.9 mg/（kg·d） ＋ Fenofibrate 18 mg/（kg·d）, respectively] were administrated drugs. TC, TG, LDLC, HDLC, ALT, AST and hs-CRP were measured at the end of the fourth and the eighth week. Results The level of TC, LDLC, TG in normal group, atorvastatin group, AFH group and AFF group were obviously lower than control group （ P 〈 0.01 ） ; That of HDLC in AFH group and AFF group were higher than atorvastatin group（ P 〈 0.01 ）. The level of hsCRP in control group, atorvastatin group, AFH group and AFF group were obviously increased than normal group（ P 〈 0.05 ）. Compared with Atorvastatin group, the level of hsCRP in AFH group and AFF group were lower. 3. The level of ALT and AST in control group, atorvastatin group, AFH group and AFF group were obviously higher than normal group （ P 〈 0.01）. Those in Atorvastatin group and AFF group were lower than Control group（ P 〈 0.01） andAFHgroup（P〈0.05）. Condusions Combination therapy of fenofibrate plus atorvastatin can strengthen the effects on decreasing lipids and the level of hs-CRP. The negative effects of combination therapy are related to the doses of fenofibrate and atorvastatin, so administrating drugs from low doses and at different time are very important to reduce hepatic damage.