Effects Of MCI-186 On Diabetic Neuropathy In Rats

Objective:To evaluate the effects of MCI-186, a free radical scavenger, on oxidative stress and poly(ADP-ribose) polymerase(PARP) activation in the dorsal root ganglions of STZ induced diabetic rats.Methods:Experimental diabetes was induced in two-month old male SD rats by intraperitoneal injection of 55mg/kg streptozotocin for 8w. Then the diabetic rats were divided into 3 groups: MCI group, normal saline (NS) group and diabetes control group MCI-186 (3mg/kg) and normal saline were injected intraperitoneally to the rats in MCI group and the NS group for 2w, respectively. No intervention was added to the diabetes control group for the later 2 weeks. At the same time, 10 normal rats were raised as normal control group.At the end of the experiment, the rats were anesthetized by intraperitoneal injection of 150mg/kg ketamine and were operated at prone position. The dorsal root ganglia (DRGs) from lumbar spine L4 - L6 of the rats were taken for the pathological study and the detection of the activation of PARP and Caspase 3.Results:Electron microscopic studies revealed a graded changes of DRG neurons with abundant vacuoles in mitochondria in NS group and diabetes group, fewer vacuoles in mitochondria were detected in MCI group while no obvious changes were found in normal control group. The expression of PARP decreased progressively in the normal control group, the MCI group, the NS group and the diabetes control group. Cleaved-PAR were found to be increased by degrees in the same order. However, fragment of Caspase 3 were failed to be find from cleavage.Conclusion:1. The pathologic changes of DRGs in STZ induced diabetic rats appeared to be neuron necrosis.2. An early stage of apoptosis might be activated.3. MCI-186 might have some protection against DPN, but have no blockage in the progress of DPN...