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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
【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。
【Abstract】 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 establishment 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,fluvastatin 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 respectively and then homeostasis model assessment of insulin resistance was calculated.RESULTS By the end of the 4th week,the metabolic 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 significantly(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.
【Key words】 fluvastatin; metabolic syndrome; insulin resistance; hs-CRP;
- 【文献出处】 中国药学杂志 ,Chinese Pharmaceutical Journal , 编辑部邮箱 ,2012年22期
- 【分类号】R965
- 【下载频次】96