Pathophysiological profiles of SDT fatty rats, a potential new diabetic peripheral neuropathy model

Autor: Hironobu Tadaki, Yu Motohashi, Shinichi Kume, Tatsuya Maekawa, Tomohiko Sasase, Katsuhiro Miyajima, Takeshi Ohta
Rok vydání: 2017
Předmět:
Zdroj: Journal of Pharmacological and Toxicological Methods. 88:160-166
ISSN: 1056-8719
DOI: 10.1016/j.vascn.2017.09.257
Popis: Introduction To establish an animal model for diabetic peripheral neuropathy (DPN) at an earlier stage, we performed functional and pathophysiological evaluations in Spontaneously Diabetic Torii (SDT) fatty rats before 16 weeks of age. Methods Male SDT fatty rats were treated with vehicle or phlorizin (100 to 150 mg/kg/day) from 5 to 16 weeks. Sprague-Dawley (SD) rats were used as age-matched controls. Body weights and biochemical parameters were measured over time. During the treatment period, the sensory and motor nerve conduction velocity (SNCV and MNCV) of the sciatic nerve, blood pressure, pupil size, and electrocardiograms were measured. At 16 weeks, the rats were sacrificed and sural nerves and intraepidermal nerves were sampled for histological studies, electron microscopic analysis and assessments of nerve fiber density. Results Functional abnormalities, such as delays of SNCV, increase of blood pressure, reduced pupillary reactivity, and decrease of the coefficient of variance of R-R intervals were observed in SDT fatty rats. Histopathologically, decreased intraepidermal nerve fiber density, mitochondrial abnormalities of small myelinated fibers, and vacuolation and mitochondrial swelling of unmyelinated fibers were found in SDT fatty rats. These changes were prevented by well-controlled blood glucose with phlorizin treatment. Discussion Male SDT fatty rats can help future work on DPN in diabetes with obesity, since this rat exhibited functional and pathological abnormalities in somatic and autonomic nerve from an early stage of diabetes.
Databáze: OpenAIRE