普伐他汀和罗苏伐他汀对实验性糖尿病大鼠模型碳水化合物代谢作用的比较。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Acta Pharmaceutica Pub Date : 2024-03-30 Print Date: 2024-03-01 DOI:10.2478/acph-2024-0001
Hacer Kayhan Kaya, Berjan Demirtas, Beran Yokus, Dilek Aygün Kesim, Ezel Tasdemir, Abdurrahman Sermet
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引用次数: 0

摘要

他汀类药物治疗可能会增加患糖尿病的风险;关于他汀类药物如何影响葡萄糖调节和血糖控制的数据尚不充分,而他汀类药物对与碳水化合物代谢有关的肝酶的影响尚未得到充分研究。因此,我们旨在比较他汀衍生物普伐他汀和罗苏伐他汀在实验性糖尿病大鼠模型中对碳水化合物代谢的影响。我们使用雌性 Wistar 白化大鼠,通过腹腔注射链脲佐菌素诱发糖尿病。此后,以口服灌胃的方式给糖尿病大鼠服用普伐他汀和罗苏伐他汀,剂量分别为 10 毫克/千克-1 天-1 和 20 毫克/千克-1 天-1,连续服用 8 周。实验结束时,测量了大鼠的体重、空腹血糖水平、血清胰岛素、胰岛素抵抗(HOMA-IR)、肝糖原和与碳水化合物代谢相关的肝酶。两种剂量的普伐他汀都能明显增加糖尿病大鼠的体重,但罗苏伐他汀,尤其是 20 毫克/公斤-1 天-1 的剂量,能明显减少体重。普伐他汀,尤其是 20 毫克/千克-1 天-1 的剂量,会导致肝糖原合成酶和葡萄糖-6-磷酸脱氢酶水平显著升高,但会导致糖原磷酸化酶、乳酸脱氢酶和葡萄糖-6-磷酸酶水平显著降低。因此,普伐他汀能部分改善糖尿病引起的肝酶的不良变化,特别是在 20 毫克/公斤-1 天-1 的剂量下,能降低空腹血糖水平,增加肝糖原含量。然而,罗伐他汀,尤其是 20 毫克/千克-1 天-1 的剂量,会显著降低糖尿病大鼠肝糖原合成酶和丙酮酸激酶的水平,但会增加糖原磷酸化酶的水平。瑞舒伐他汀(20 毫克/千克-1 天-1 次)能显著降低糖尿病大鼠的体重和肝糖原含量。由此可以得出结论,普伐他汀(尤其是 20 毫克/公斤-1 天-1 的剂量)通过调节碳水化合物代谢,能更有效地改善糖尿病的负面影响。
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Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.

Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg-1 day-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg-1 day-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg-1 day-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg-1 day-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg-1 day-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg-1 day-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg-1 day-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.

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来源期刊
Acta Pharmaceutica
Acta Pharmaceutica PHARMACOLOGY & PHARMACY-
CiteScore
5.20
自引率
3.60%
发文量
20
审稿时长
>12 weeks
期刊介绍: AP is an international, multidisciplinary journal devoted to pharmaceutical and allied sciences and contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell biology, cell cultures, clinical pharmacy, drug design, drug delivery, drug disposition, drug stability, gene technology, medicine (including diagnostics and therapy), medicinal chemistry, metabolism, molecular modeling, pharmacology (clinical and animal), peptide and protein chemistry, pharmacognosy, pharmacoepidemiology, pharmacoeconomics, pharmacodynamics and pharmacokinetics, protein design, radiopharmaceuticals, and toxicology.
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