Modeling long-term diabetes and related complications in rats

作者：Hajna Zsofia; Szabadfi Krisztina; Balla Zsolt; Biro Zsolt; Degrell Peter; Molnar Gergo A; Koszegi Tamas; Tekus Valeria; Helyes Zsuzsanna; Dobos Andras; Farkas Sandor; Szucs Gyula; Gabriel Robert; Pinter Erika^*

来源：Journal of Pharmacological and Toxicological Methods, 2016, 78: 1-12.

DOI：10.1016/j.vascn.2015.11.003

• Anterior segment neovascularization
• Chronic model
• Cold allodynia
• Diabetic nephropathy
• Diabetic neuropathy
• Diabetic retinopathy
• Drug development
• Insulin implant
• Preclinical model
• Streptozotocin

Introduction: Accurate preclinical modeling of diabetic complications such as retinopathy, nephropathy and neuropathy is crucial to enable the development of novel preventative therapies. The aims of this study were to establish a model of long-term diabetes with sustained medium scale hyperglycemia and characterize the pathological changes detectable after 4 months, with particular respect to dependence on the degree of hyperglycemia.
Methods: Streptozotocin-induced diabetic CFY rats were subjected to four different insulin substitution protocols to achieve different levels of glycemic control (Diabetic 1-4 groups). Eyes were investigated by ophthalmoscopy, kidney function by urine analysis, and neuropathy by functional tests. Retinal and renal morphological evaluations were performed by histology, immuno-histochemistry and electron microscopy.
Results: Rats of the Diabetic 3 group showed massive hyperglycemia-dependent anterior segment neovascularization, enhanced total retinal score and retinal apoptotic cell number, degeneration of dopaminergic amacrine cells, increased glomerular PAS-positivity, altered excreted total protein/creatinine ratio and cold allodynia, parallel with medium scale hyperglycemia (blood glucose level between 22 and 25 mmol/L) and satisfying state of health.
Discussion: We established a treatment protocol in rats enabling complex investigation of diabetic retinopathy, nephropathy and neuropathy on a long-termperiod. Clearly hyperglycemic dependent parameters of these complications serve as good outcome measures for preclinical trials. Our results provide a useful basis for designing studies for testing preventative treatments as well as other translational medical research in this field.

• 出版日期2016-4