[目的]探讨成纤维细胞生长因子-21(FGF21)对糖尿病Beagle犬的降糖作用。[方法]通过注射四氧嘧啶(ALX)50 mg/kg和链脲霉素(STZ)30 mg/kg溶液,建立糖尿病Beagle犬动物模型。糖尿病模型复制成功后,考察25μg/kg、50μg/kg和100μg/kg的FGF21以及阳性对照50μg/kg的地特胰岛素注射液(Det),每72 h给药1次,连续给药10次后,对糖尿病Beagle犬血糖等生化指标和肝脏、胰腺组织切片的影响。[结果]与模型组相比,FGF21各剂量给药组Beagle犬体重呈现升高趋势(p〈0.05),各给药组血糖、糖化血红蛋白水平均显著降低,并呈剂量依赖性,即随着FGF21给药剂量的增加,治疗效果更明显,其中高剂量组治疗效果最佳,治疗后空腹血糖达到8.77±5.74 mmol/L,糖化血红蛋白浓度4.89±1.36%,C肽浓度为0.010±0.000 nmol/L,与模型组存在显著差异(p〈0.01、p〈0.05、p〈0.01)。FGF21各剂量组肝脏和胰腺组织病变程度明显减轻。[结论]FGF21对Beagle犬有明显的降低血糖作用,FGF21各剂量组肝脏和胰腺组织病变程度明显减轻,为糖尿病治疗提供了新思路。
[Objective]To investigate the hypoglycemic effects of FGF21 on diabetic beagle dogs.[Methods]The diabetic beagle animal model was established by injecting 50 mg / kg alloxan( ALX) and 30 mg / kg streptozotocin( STZ) solution. After the success of the diabetes model replication,the diabetes of beagle dogs were administered with different doses of FGF21( 25 μg / kg,50μg /kg- 1and 100 μg / kg) or 50 μg / kg insulin as positive control for 4 weeks. The changes of the weight,blood glucose,glycosylated hemoglobin,liver tissues and pancreatic tissues of beagle dogs were observed after drug treatment. [Results]Data showed that,compared with the model group,FGF21 displayed a significant increase in the body weights and significant reduction in blood glucose,glycosylated hemoglobin levels and showed a dose- dependent features. In addition,the injure in liver and pancreatic tissues of FGF21 were significantly alleviated which was confirmed by pathological morphology reversion.[Conclusion]FGF21 had obvious hypoglycemic effect on lowering the blood glucose level of diabetic beagle dogs,the injure in liver and pancreatic tissues of FGF21 were significantly alleviated which was confirmed by pathological morphology reversion,providing a new idea for the treatment of diabetes.