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目的探讨不同剂量和剂型的氟伐他汀对代谢综合征(metabolic syndromes,MS)小鼠胰岛素抵抗(insulin resistance,IR)及超敏C反应蛋白(hs-CRP)的影响。方法 60只雄性SPF级KM小鼠随机分为2组,正常对照组10只,模型组50只,正常对照组给予正常饮食,模型组给予高热量饮食,4周末模型组随机抽取10只,检测MS模型建立,第5周开始剩余40只随机分为A、B、C、D 4组,均给予正常饮食,分别给予氟伐他汀胶囊6 mg·kg-1·d-1,氟伐他汀胶囊12 mg·kg-1·d-1,氟伐他汀缓释片12 mg·kg-1·d-1,生理盐水灌胃,8周末检测血脂(TC、TG、LDL-C、HDL-C)、hs-CRP、空腹血糖(FBG)、血清胰岛素(FINS),以及计算稳态模型胰岛素抵抗评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)。结果 4周末计算模型组HOMA-IR增高,即形成胰岛素抵抗,成功建立代谢综合征模型,8周末A、B、C 3组与D组比较,TC、TG和LDL-C水平均明显降低(P<0.01);HDL-C水平显著升高(P<0.05);hs-CRP、FBG和FINS水平也明显下降(P<0.01)。B组与A组比较,TC、TG、LDL-C水平下降更为显著(P<0.05),而hs-CRP、FBG和FINS水平则无明显变化;而C组与B组相比,TC、TG、LDL-C和hs-CRP、FBG、FINS水平均明显降低(P<0.05),HOMA-IR也明显下降(P<0.05)。结论氟伐他汀可降低MS小鼠TC、TG、LDL-C、FINS、hs-CRP,改善IR,且随剂量的增加和剂型的改善作用更为明显。其作用机制可能与抗炎作用有关。
Objective To investigate the effects of fluvastatin with different dosages and dosage forms on insulin resistance (IR) and hs-CRP in metabolic syndromes (MS) mice. Methods Sixty male SPF KM mice were randomly divided into two groups: normal control group (n = 10), model group (n = 50) and normal control group (n = 10). The model group was given high calorie diet. MS model was established. The remaining 40 mice were randomly divided into A, B, C and D 4 groups at the beginning of the fifth week, and were given normal diet. Fluvastatin capsule was given 6 mg · kg -1 · d -1, (TC, TG, LDL-C and HDL-C) at 12 and 12 mg · kg-1 · d-1 and 12 mg · kg -1 · d -1 fluvastatin sustained- , Hs-CRP, fasting blood glucose (FBG), serum insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Results At the end of the 4th week, HOMA-IR increased and insulin resistance was formed in the model group. Metabolic syndrome model was successfully established. At the 8th weekend, the levels of TC, TG and LDL-C in group A, B and C were significantly lower than those in group D <0.01). The levels of HDL-C were significantly increased (P <0.05), and the levels of hs-CRP, FBG and FINS were also significantly decreased (P <0.01). The levels of TC, TG and LDL-C in group B were significantly lower than those in group A (P <0.05), while the levels of hs-CRP, FBG and FINS in group B were not significantly different. TG, LDL-C and hs-CRP, FBG and FINS were significantly decreased (P <0.05), HOMA-IR was also significantly decreased (P <0.05). Conclusions Fluvastatin can reduce TC, TG, LDL-C, FINS and hs-CRP in MS mice and improve IR, and the effect of fluvastatin is more obvious with dose increasing and dosage form improving. Its mechanism may be related to anti-inflammatory effects.