阿托伐他汀联合非诺贝特对混合性高脂血症大鼠的疗效及其骨骼肌的影响

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治疗混合性高脂血症大鼠的较佳给药剂量、方法及对骨骼肌的影响。方法60只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),晚间给药]、AFF组[阿托伐他汀0.9mg/(kg·d)+非诺贝特18mg/(kg·d),早晚分开给药]及AFH组[阿托伐他汀0.9mg/(kg·d)+非诺贝特18mg/(kg·d),晚间同时给药],造模4周,用药4周。采血检测TC、TG、LDLC、HDLC、CK、Mb及K+。结果AFF组和AFH组较阿托伐他汀组更加有效的降低LDLC和TG(P<0.01),升高HDLC(P<0.01)。AFH组的CK、Mb及K+水平明显升高(P<0.01)。结论阿托伐他汀与非诺贝特联合较加倍剂量的阿托伐他汀增强全面调脂疗效;二者早晚分开给药,可以减少对骨骼肌的影响。

Objective To evaluate the efficacy and safety of combination therapy with atorvastatin plus fenofibrate in rats with combined hyperlipidemia. Methods Sixty Wistar rats were randomized into normal group, control group, atorvastatin group, AFH group and AFF group, and fed with high fatty food, except for normal group. At end of week 4, rats in atorvastatin group were given atorvastatin [ 1.8mg/（ kg · d） ], rats in AFH group were administered atorvastatin [0.9mg/（ kg · d） ＋ fenofibrate [ 18mg/（ kg · d） ], and rats in AFF group received atorvastatin [0.9mg/（kg· d）＋ fenofibrate 18mg/（kg· d）]. Levels of TC, TG, LDLC, HDLC, CK, Mb, K ^＋ were measured at the end of weeks 4 and 8, respectively. Results The levels of LDLC, and TG were obviously lower in AFH and AFF groups than in atorvastatin group （ P 〈 0. 01 ）. However, the level of HDLC was higher in AFH and AFF groups than in atorvastatin group（P 〈 0. 01 ）. The level of CK, Mb, K ^＋ was significantly higher in AFH group than in other groups （ P 〈 0.01 ）. Conclusion Combination therapy with atorvastatin plus fenofibrate can decrease the TG and LDLC level, and increase the HDLC level. The negative effects of combination therapy are related to the doses of fenofibrate and atorvastatin, thus drugs should be administered from low to high doses in order to reduce the CK, Mb and K ＋ level.