阿托伐他汀对新西兰兔胰岛素敏感性的短期影响
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摘要
目的研究阿托伐他汀对新西兰兔胰岛素敏感性的急性影响。方法 3月龄健康雄性新西兰大耳白兔40只,随机分为对照组、阿托伐他汀5mg/(kg·d)组(A组),阿托伐他汀10mg/(kg·d)组(B组),阿托伐他汀20mg/(kg·d)组(C组),每组10只。喂养3d后,于第4天清晨空腹采血测定血糖及血清胰岛素(FINS)浓度,计算胰岛素敏感指数(ISI),并行静脉葡萄糖耐量试验(IVGTT),于0、5、15、30、60、120min采血分离血清测定血糖、血清胰岛素水平。结果与对照组比较,阿托伐他汀组空腹血糖及FINS水平升高(P<0.05),A组、B组、C组ISI则明显降低[ln{ISI[(mmol/L)·(mU/L)]~(-1)}-4.19±0.22、-4.31±0.19、-4.42±0.12比-3.97±0.21,均P<0.05];在IVGTT中,A组、B组、C组的血糖下降迟缓,胰岛素分泌高峰值低于对照组,达峰时间延迟。结论高剂量阿托伐他汀[10~20mg/(kg·d)]能够影响新西兰兔的糖代谢,降低胰岛素敏感性,且随阿托伐他汀剂量的增加,影响越明显。
Objective To evaluate the short-term effect of atorvastatin on insulin sensitivity in New Zealand rabbits.Methods Forty male New Zealand white rabbits(3 months old)were randomly divided into 4 groups:normal control group;5 mg/(kg·d)atorvastatin group(Group A);10 mg/(kg·d)atorvastatin group(Group B)and 20 mg/(kg·d)atorvastatin group(Group C)with n=10 in each group. After feeding with atorvastatin at different doses in each group for three days,in the morning of the following day,the levels of fasting blood glucose,fasting serum insulin(FINS)were measured and insulin sensitivity index(ISI)was calculated. And then intravenous glucose tolerance test was performed with the levels of blood glucose and serum insulin measured at different time points thereafter. Results Compared with the normal control group,the levels of fasting blood glucose and serum insulin in atorvastatin treated groups were significantly increased(P<0.05)and the ISI was significantly reduced in group A,group B,and group C [ln{ISI[(mmol/L)·(mU/L)]~(-1)}:-4.19±0.22,-4.31±0.19,-4.42±0.12 vs-3.97±0.21,all P<0.05].In IVGTT,compared with normal control group,blood glucose declined slower,and the peak value of insulin secretion decreased significantly in group A,group B,group C,and the time to peak was delayed as well. Conclusion High-dose[10-20 mg/(kg·d)]atorvastatin could affect glucose metabolism,and decrease insulin sensitivity in New Zealand rabbits. The impact was significant with the increase of the dose of atorvastatin.
Objective To evaluate the short-term effect of atorvastatin on insulin sensitivity in New Zealand rabbits.Methods Forty male New Zealand white rabbits(3 months old)were randomly divided into 4 groups:normal control group;5 mg/(kg·d)atorvastatin group(Group A);10 mg/(kg·d)atorvastatin group(Group B)and 20 mg/(kg·d)atorvastatin group(Group C)with n=10 in each group. After feeding with atorvastatin at different doses in each group for three days,in the morning of the following day,the levels of fasting blood glucose,fasting serum insulin(FINS)were measured and insulin sensitivity index(ISI)was calculated. And then intravenous glucose tolerance test was performed with the levels of blood glucose and serum insulin measured at different time points thereafter. Results Compared with the normal control group,the levels of fasting blood glucose and serum insulin in atorvastatin treated groups were significantly increased(P<0.05)and the ISI was significantly reduced in group A,group B,and group C [ln{ISI[(mmol/L)·(mU/L)]~(-1)}:-4.19±0.22,-4.31±0.19,-4.42±0.12 vs-3.97±0.21,all P<0.05].In IVGTT,compared with normal control group,blood glucose declined slower,and the peak value of insulin secretion decreased significantly in group A,group B,group C,and the time to peak was delayed as well. Conclusion High-dose[10-20 mg/(kg·d)]atorvastatin could affect glucose metabolism,and decrease insulin sensitivity in New Zealand rabbits. The impact was significant with the increase of the dose of atorvastatin.
引文
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[2]张秋兰,晋万强,赵静茜.瑞舒伐他汀、普伐他汀对轻中度原发性高血压患者冠状动脉粥样硬化的影响[J].中华高血压杂志,2010,18(4):357-360.
[3]Armitage J.The safety of statins in clinical practice[J].Lancet,2007,370(9601):1781-1790.
[4]Sattar N,Preiss D,Murray HM,et al.Statins and risk of incident diabetes:a collaborative meta-analysis of randomised statin trials[J].Lancet,2010,375(9716):735-742.
[5]Jo A,Ko M,Kim Y,et al.Statin use and risk of new-onset type2diabetes mellitus and cardiovascular disease:a nationwide population-based observational study using national claim data[J].Value Health,2015,18(7):382.
[6]Ridker PM,Danielson E,Fonseca FA,et al.Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein[J].N Engl J Med,2008,359(21):2195-2207.
[7]Nakata M,Nagasaka S,Kusaka I,et al.Effects of statins on the adipocyte maturation and expression of glucose transporter 4(SLC2A4):implications in glycaemic control[J].Diabetologia,2006,49(8):1881-1892.
[8]Berthold HK,Naini A,Di Mauro S,et al.Effect of ezetimibe and/or simvastatin on coenzyme Q10levels in plasma:a randomised trial[J].Drug Saf,2006,29(8):703-712.
[9]Kawashiri MA,Nohara A,Tada H,et al.Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10in heterozygous familial hypercholesterolemia:results from a crossover study[J].Clin Pharmacol Ther,2008,83(5):731-739.
[10]Kostapanos MS,Milionis HJ,Elisaf MS.An overview of the extra-lipid effects of rosuvastatin[J].J Cardiovasc Pharmacol Ther,2008,13(3):157-174.
[11]US Food and Drug Administration.FDA drug safety communication:important safety label changes to cholesterol-lowering statin drugs[EB/OL].[2012-02-28].http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm.