不同剂量和剂型的氟伐他汀对代谢综合征小鼠糖代谢的影响  

Effects of Different Dosages of Fluvastatin from Different Dosage Forms on Glycometabolism in Rats with Metabolic Syndromes

作　　者：张雪娟[1] 宋力[1] 平立风[1] 孙希美[1] 李国梁[1] 

机构地区：[1]青岛大学医学院附属医院心内科,山东青岛266003

出　　处：《中国药学杂志》2012年第22期1821-1824,共4页Chinese Pharmaceutical Journal

摘　　要：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 evaluate the effects of fluvastatin on insulin resistance and hs-CRP level in metabolic syndrome rat model. METHODS Sixty male KM rats were randomly divided into two groups ： 10 rats in control （ normal diet） and 50 rats in model （ high lipid diet） group. By the end of the 4th week, 10 rats selected randomly from the model group were killed to verify the establish- ment of metabolic syndrome model. Since the 5th week, the remainder 40 rats were randomly divided into A, B, C and D groups, then were administered intragastrically with fluvastatin capsules at 6 mg · kg-1 · d-1 , fluvastatin capsules at 12 mg · kg-1 · d-1 , fluvasta- tin slow-release tablets at 12 mg · kg-1 · d-1 and saline, respectively, and all the rats were fed on normal diet for 4 weeks. All the rats were killed by the end of the 8th week. The levels of TC, TG, LDL-C, HDL-C, FBG, FINS, and hs-CRP were measured respec- tively and then homeostasis model assessment of insulin resistance was calculated. RESULTS By the end of the 4th week, the meta- bolic syndromes model was established. At the end of the experiment, compared with group D, the levels of TC,TG and LDL-C were decreased significantly（ P 〈 0. 01 ） while HDL-C were increased significantly in A, B and C groups （P 〈 0. 05 ） ;the levels of hs-CRP, FBG and FINS were decreased significantly（P 〈 0. 01 ）. Compared with group A, the levels of TC, TG and LDL-C were decreased sig- nificantly（P 〈0.05） ,while the levels of hs-CRP, FBG and FINS had no change in group B（P 〉0. 05） ; compared with group B, the levels of TC, TG, LDL-C, hs-CRP, FBG, FINS and HOMA-IR were decreased significantly in group C （P 〈 0. 05）. CONCLUSION Fluvastatin can reduce TC, TG, LDL-C, FINS, and hs-CRP levels and improve insulin resistance, the effects is more apparent at a large-dosage and with slow-release tablets especially, and that may attribute to its anti-inflammation effects.

关 键 词：氟伐他汀 代谢综合征 胰岛素抵抗 超敏C反应蛋白 

分 类 号：R944[医药卫生—药剂学] R965[医药卫生—药学]