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阿托伐他汀联合羟氯喹对四氧嘧啶诱导糖尿病大鼠血糖的影响。

Effect of atorvastatin and hydroxychloroquine combination on blood glucose in alloxan-induced diabetic rats.

机构信息

Department of Medical Affairs and Clinical Research, Ipca Laboratories Ltd., 142 AB, Kandivli Industrial Estate, Kandivli (West), Mumbai - 400 067, India.

出版信息

Indian J Pharmacol. 2009 Jun;41(3):125-8. doi: 10.4103/0253-7613.55213.

Abstract

OBJECTIVE

To evaluate the antihyperglycemic activity of atorvastatin and hydroxychloroquine combination in alloxan-induced diabetic rats.

MATERIALS AND METHODS

Alloxan induced diabetic Wistar male rats were randomized into six groups of 6 rats each. (Normal rats, diabetic control, atorvastatin (ATV), hydroxychloroquine (HCQ), ATV 5 mg /kg + HCQ 100 mg/kg, and ATV 10 mg/kg + HCQ 200 mg/kg). The rats were treated for 9 days and blood samples were collected at baseline and end of therapy. These samples were analyzed for plasma glucose by autoanalyzer. Changes in body weight, water, food intakes and total protein content were also recorded.

RESULTS

Atorvastatin and hydroxychloroquine alone and in combination reported significant fall in blood glucose level from baseline. Fall in glucose level was significantly more in high dose combination of atorvastatin and hydroxychloroquine (ATV: 10 mg/kg + HCQ: 200 mg/kg) as compared to other study treatment groups (ATV: 17% Vs HCQ: 7% Vs ATV 5mg/kg + HCQ 100mg /kg: 14% Vs ATV 10mg/kg + HCQ 200mg /kg: 21%; p<0.01). ATV and HCQ individually and in combination also improved the body weight loss. The weight gain was significantly more in combination treated rats as compared to positive control group and greater than those who received atorvastatin and hydroxychloroquine alone. Rats treated with the combination also reported significant decrease in food intake and significant increase in total protein.

CONCLUSION

Increased hypoglycemic effect in combination may be due to potentiation or synergism between HCQ and ATV. Further studies are required to demonstrate clinically significant antidiabetic effect.

摘要

目的

评估阿托伐他汀和羟氯喹联合在四氧嘧啶诱导的糖尿病大鼠中的降血糖活性。

材料和方法

将四氧嘧啶诱导的糖尿病 Wistar 雄性大鼠随机分为 6 组,每组 6 只(正常大鼠、糖尿病对照组、阿托伐他汀(ATV)、羟氯喹(HCQ)、ATV5mg/kg+HCQ100mg/kg 和 ATV10mg/kg+HCQ200mg/kg)。大鼠治疗 9 天,在基线和治疗结束时采集血样。用自动分析仪分析血浆葡萄糖。还记录了体重、水、食物摄入量和总蛋白含量的变化。

结果

阿托伐他汀和羟氯喹单独和联合使用均能显著降低血糖水平。与其他研究治疗组相比,阿托伐他汀和羟氯喹高剂量联合(ATV:10mg/kg+HCQ:200mg/kg)降低血糖水平更为显著(ATV:17%比 HCQ:7%比 ATV5mg/kg+HCQ100mg/kg:14%比 ATV10mg/kg+HCQ200mg/kg:21%;p<0.01)。阿托伐他汀和羟氯喹单独和联合使用也改善了体重减轻。与阳性对照组相比,联合治疗组的体重增加更为显著,且大于单独使用阿托伐他汀和羟氯喹的体重增加。联合治疗组的大鼠还报告了食物摄入量显著减少和总蛋白显著增加。

结论

联合用药的降血糖作用增强可能是由于 HCQ 和 ATV 之间的增效或协同作用。需要进一步的研究来证明其具有临床意义的抗糖尿病作用。

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