ABSTRACT
Objective To prepare the rat model of type 2 diabetes mellitus (T2DM), and to ob-serve the characteristics of peripheral neuropathy. Methods High fat and high sugar diets were fed for 8 weeks to induce insulin resistance and then low dose streptozotocin ( STZ) was injected intraperitoneally to induce type 2 diabetes mellitus models in Sprague Dawley rats. Blood glucose and serum insulin levels con-tinuous were monitored. Tactile allodynia in response to von Frey ( VF) filament stimulation of the plantar hind paws and paw withdrawal thermal latency ( PWTL) to plantar test were used as the criterion for diabetic neuropathy. Instruments AD was used to detect nerve conduction velocity ( NCV) of sciatic nerve in rat and the morphological and pathological changes of sciatic nerve were detected by electron microscope. Results The characteristics of T2DM rats by peripheral neuropathy in this method were that 50％ force withdrawal threshold and PWTL were measured. Both values of diabetic rats were decreased from the day of STZ injec-tion until 4 weeks after STZ injection, and then increased 8 weeks after STZ injection (50％ force withdraw-al threshold values, (11.8 ±0.8)g, (8.4 ±0.7)g and (16.2 ±1.4)g; PWTL (10.2 ±0.9)s, (8.3 ± 1. 2)s and (13. 2 ± 1. 0)s. These results indicated that tactile sensation changed from hypersensitive to hy-posensitive. Compared to the NC group, the sciatic nerve motor and sensory conduction velocity were signifi-cantly decreased at 4 and 8 weeks in DM group, respectively. Compared to DM group at 4 weeks, the sciat-ic nerve motor and sensory conduction velocities were further decreased in the DM group at 8 weeks. Con-clusively, sciatic nerve showed obvious demyelination and axonal collapse. Conclusions T2DM rat model was successfully induced by high fat and sugar diet combined with small dose of STZ injection. The rat mod-el has typical pathological change of peripheral nerve. It might provide a particularly advantageous tool for investigations of diabetes and its chronic complications.
ABSTRACT
Objective To investigate the dynamic changes of endoplasmic reticulum stress-related molecules including glucose regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12 in sciatic nerve of diabetic rats and explore its mechanisms.Methods Rats were randomly divided into normal control group (NC) and diabetes mellitus group (DM) that were induced by intraperitoneal injection of Streptozocin after 4 weeks of high-fat chow feeding.Sciatic nerves were isolated for three times at 4 weeks, 8 weeks and 12 weeks after induction of diabetes.The expressions of GRP78, CHOP,and caspase-12 were detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.The morphology of sciatic nerve was investigated with electron microscope.Results With the extension of the course, demyelinating and axonal injury appeared in sciatic nerve of diabetic rats.The expressions of GRP78 mRNA and protein in DM group were significantly higher than NC group at 4 weeks and 8 weeks after induction of diabetes(P ＜0.05, P ＜0.01).The expressions of CHOP mRNA and protein in DM group were significantly higher than NC group at 8 weeks and 12 weeks after induction of diabetes (P ＜ 0.05).The expressions of caspase-12 mRNA and protein in DM group were significantly higher than NC group at 8 weeks after induction of diabetes(P ＜ 0.05, P ＜ 0.01).Conclusions Endoplasmic reticulum stress-related molecules (GRP78, CHOP, and caspase-12) contributed to the peripheral nerve injury of diabetic rats, and displayed dynamic changes.