[1]王颖,常宝成,单春艳,等.阿托伐他汀对大鼠胰岛功能影响的量效和时效关系[J].国际内分泌代谢杂志,2017,37(04):221-226.
　Wang Ying*,Chang Baocheng,Shan Chunyan,et al.Dose-effects and time-effects of atorvastatin on islet function of rats[J].International Journal of Endocrinology and Metabolism,2017,37(04):221-226.
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阿托伐他汀对大鼠胰岛功能影响的量效和时效关系()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年04期
页码:
221-226
栏目:
论著
出版日期:
2017-07-20

文章信息/Info

Title:
Dose-effects and time-effects of atorvastatin on islet function of rats
作者:
王颖; 常宝成; 单春艳; 郑妙艳; 杨菊红; 陈莉明; 李鹤超
天津医科大学代谢病医院糖尿病肾病科,内分泌研究所,卫生部激素与发育重点实验室,天津市代谢性疾病重点实验室
Author(s):
Wang Ying*;  Chang Baocheng;  Shan Chunyan;  Zheng Miaoyan;  Yang Juhong;  Chen Liming;  Li Hechao.
*Department of Diabetic Nephropathy, Key Laboratory of Hormones and Development(Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, The Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China
关键词:
阿托伐他汀;  胰岛素敏感性;  胰岛功能;  大鼠
Keywords:
Atorvastatin;  Insulin sensitivity;  Islet function;  Rat
文献标志码:
A
摘要:
目的 观察阿托伐他汀对Wistar大鼠胰岛功能及糖耐量的影响,研究其效应与剂量、时间的相关性。方法 将60只8周龄正常Wistar大鼠采用随机数字表法分为正常对照组(生理盐水2 ml/d,n=10)、低剂量阿托伐他汀组(阿托伐他汀5 mg·kg-1·d-1,n=10)、中剂量阿托伐他汀组(阿托伐他汀25 mg·kg-1·d-1,n=10)和高剂量阿托伐他汀组(阿托伐他汀50 mg·kg-1·d-1,n=30)。于干预第0、4、8周分别行口服葡萄糖耐量试验(OGTT),测定血糖、血清胰岛素,计算稳态模型评估-β细胞功能指数(HOMA-β)、第一时相胰岛素分泌指数(△I30/△G30)、稳态模型评估-胰岛素抵抗指数(HOMA-IR)、胰岛素曲线下面积(AUCi)、葡萄糖曲线下面积(AUCg)和处置指数。然后将高剂量阿托伐他汀组部分大鼠采用随机数字表法分为两组,继续给药组仍给予高剂量阿托伐他汀灌胃,洗脱组改为生理盐水灌胃,4周后再次行OGTT检测。并取血行甘油三酯、总胆固醇检测。结果 干预8周后高剂量阿托伐他汀组OGTT 0、15、30、60、120 min的胰岛素水平及HOMA-β、△I30/△G30、AUCi、AUCg、HOMA-IR均低于正常对照组(F=4.168～306.493,P均<0.05); 干预4周时各组及干预8周时中、低剂量阿托伐他汀组均未见相似效应(P均>0.05)。经4周药物洗脱期后,洗脱组的OGTT 0、15、30、60、120 min胰岛素水平(F=4.64～15.58,P均<0.05)及上述指标均高于继续给药组(t=29.044、4.433、4.429、2.964,P均<0.05)。但各剂量阿托伐他汀组间血糖和处置指数均未见明显影响(P均>0.05)。HOMA-β、△I30/△G30、AUCi随阿托伐他汀剂量的增加和时间的延长,均逐渐降低,具有剂量及时间依赖关系(F=213.970、63.839、18.222,P均<0.01)。HOMA-IR、AUCg随阿托伐他汀剂量的增加逐渐降低,随着时间的延长逐渐升高,也呈剂量及时间依赖关系(F=214.437,P<0.01; F=9.33,P<0.05)。结论 阿托伐他汀可抑制大鼠胰岛β细胞胰岛素分泌,改善胰岛素敏感性,并与给药剂量和时间有关,但对血糖影响不明显。
Abstract:
Objective To study the effects of atorvastatin on islet function and glucose tolerance, investigate the dose-effects and time-effects of atorvastatin in Wistar rats.Methods Sixty eight-week-old healthy Wistar rats were divided into normal control group(physiological saline 2 ml/d, n=10), low-dose atorvastatin group(atorvastatin 5 mg·kg-1·d-1,n=10), middle-dose atorvastatin group(atorvastatin 25 mg·kg-1·d-1,n=10)and high-dose atorvastatin group(atorvastatin 50 mg·kg-1·d-1,n=30)by random number table method. An oral glucose tolerance test(OGTT)was carried out at 0, 4th, 8th week, and the levels of blood glucose and serum insulin were measured. Homeostasis model assessment-β function(HOMA-β), first-phase insulin secretion(△I30/△G30), homeostasis model assessment-insulin resistance(HOMA-IR),area under the curve of blood insulin(AUCi),area under the curve of blood glucose(AUCg)and simple glucose disposition index(DI)were calculated. Some rats in high-dose atorvastatin group were further divided into atorvastatin-continued administration group(fed with high dose atorvastatin)and atorvastatin-elution group(fed with saline)by random number table method. OGTT was carried out in these two groups after 4 weeks. The serum were collected to measure triglyceride and total cholesterol.Results After 8 weeks of intervention,compared with normal control group, the level of serum insulin at any time point(0, 15, 30, 60, 120 min)during OGTT, △I30/△G30, AUCi, AUCg, HOMA-IR were decreased in high-dose atorvastatin group(F=4.168-306.493, all P<0.05). No similar effects were observed after 4 weeks of intervention in any atorvastain group, or after 8 weeks in the middle-dose or low-dose atorvastatin group(all P>0.05). After 4 weeks atorvastatin elution, compared with atorvastatin-continued administration group, the level of serum insulin at any time point(0, 15, 30, 60, 120 min)during OGTT were higher in atorvastatin-elution group(F=4.64-15.58, allP<0.05), and other index mentioned above were higher in atorvastatin-elution group too(t=29.044, 4.433, 4.429, 2.964 respectively, all P<0.05). But atorvastatin at any dose group showed no obvious difference in blood glucose level and DI(all P>0.05).HOMA-β, △I30/△G30 and AUCi decreased gradually with the increase of atorvastatin dose and the prolongation of the experimental time, and had a dose- and time-dependent manner(F=213.970, 63.839, 18.222, all P<0.01). HOMA-IR and AUCg decreased gradually with the increase of atorvastatin dose, and increased gradually with the prolongation of the experimental time, also in a dose- and time-dependent manner(F=214.437, P<0.01; F=9.33, P<0.05).Conclusion Atorvastatin inhibits insulin secretion and increases insulin sensitivity in dose and time-response manner, without obvious effects on blood glucose.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81373864); 天津市自然科学基金资助项目(10JCYBJC13200); 天津市卫生局科技基金资助项目(2010KZ88); 天津医科大学科学基金项目(2015KYZM03)
通信作者:李鹤超, Email: hechao_li@126.com
更新日期/Last Update: 2017-07-30