| Diabetic peripheral neuropathy (DPN) is a kind of clinical symptoms or signs with peripheral nerve dysfunction due to the deficiency of secreted insulin or insulin resistance. DPN is one of the most common chronic complications of diabetes. According to the statistics report, more than30%of diabetic patients experience DPN, and the incidence of DPN can be raised to60%-90%along with the progression of diabetes. However, the exact pathogenesis of DPN is poorly understood yet. Numerous reasons might be involved in the occurrence of DPN, including metabolic disorders caused by hyperglycemia, vascular injury, decreased neurotrophic factor secretion, abnormal cytokine and oxidative stress in diabetic patients. DPN always happens bilateral and symmetrical, and results in the damage in femoral nerve, median nerve and sciatic nerve. The typical symptoms of DPN are allodynia and hyperalgesia, which seriously influence patients’ motor and sensory functions, damage their physical and mental health, lower their life quality, and even endanger their lives. The major methods for the attenuation of DPN in clinics include controlling the glucose levels, nourishing nerves and improving the microcirculation. However, the limited therapeutic effects, obvious side effects of the steep prices are the major obstacles of these drugs. Therefore, exploring more effective and safer therapeutic methods for DPN has become the extensive concerns from both research scientists and clinical staff.Recently, the biological effects of electromagnetic fields have become a hot topic in the fields of biomedical engineering. Numerous in vivo studies have shown that pulsed electromagnetic fields (PEMF) with low intensity and low frequency exhibit significant positive effects on accelerating the healing of bone fractures and soft tissue wounds, regulating microcirculation, glucose and lipid metabolisms, as well as relieving pains. Furthermore, these therapeutic effects of PEMF have also been confirmed in numerous clinical trials. Together, all these findings revealed that PEMF, as a safe, noninvasive and economic physical method has the potential to be widely employed for the treatment of varieties of diseases in clinics.It’s regarded that the biological effects of electromagnetic fields are regulated by the application of their parameters, such as the waveform, magnitude, frequency and duty circle. It’s believed that there exists obvious ’biological window’ for all these characteristic parameters of electromagnetic fields. Therefore, electromagnetic fields with different parameters may produce dramatically different, even opposite biological effects. In most previous studies, the most common problem was insufficient measurement and description for the spatial distribution of their applied electromagnetic fields, which were produced by variant magnetic field generators, resulting in reduced experimental repeatability and scientific values. Therefore, it is important to normalize the exposure conditions of electromagnetic fields and characterize the spatial distribution of the electromagnetic fields. The main subject of this research and the results are as follows:1. To meet the needs of the basic experiments of biological effects of electromagnetic fields, we developed a new magnetic generating device with a three-array coil model to produce electromagnetic fields with much more uniform spatial distribution. A finite element numerical simulation model based on COMSOL Multiphysics software was built, and the spatiotemporal distribution of magnetic fields was quantified. The results indicated that our three-array coils could generate magnetic fields with much higher magnitude and more uniform spatial distribution. It provides a new experimental platform for the studies of the biological effects of electromagnetic fields, new ideas and methods to measure the spatial and temporal distribution of magnetic field. Therefore, this study is expected to provide basis for the experiment design in the studies of biological effects of electromagnetic fields.2. Using the electromagnetic field generating device designed by our team, the present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (8in each group):the non-diabetic control group (Control), diabetes mellitus with15Hz PEMF exposure group (DM+PEMF), which were subjected to daily8-h PEMF exposure for7weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. the change of mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT) of rat were detected at0,1,3,5and7weeks after the electromagnetic field intervention were applied respectively. At the end of the experiment, rat sciatic nerve was observed by transmission electron microscope. Meanwhile, to explore the possible mechanism of pulsed electromagnetic fields on Diabetic peripheral neuropathy, immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. The results show that the blood glucose of rats increased rapidly after72h of injection which indicate the model were established successfully. During7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN(P>0.05). Compared with the control group, the, the MWT and TWT of DM group decreased significantly(P<0.05), indicating that the DPN were appeared; the MWT and TWT of DM+PEMF group also declined(P<0.05), but significantly higher than DM group(P<0.05), indicating that pulsed electromagnetic fields can improve hyperalgesia and allodynia induced by DPN. Ultrastructure observation of sciatic nerve showed that in DM group, some evidences of axonal degeneration such as demyelination and axon enlargement were observed. In DM+PEMF group, myelin sheath of sciatic nerve was also abnormal, but the damage was slighter than in the DM group. These indicate seven-week exposure to PEMF stimulation partially prevented the development of axonal degeneration in STZ-treated rats with DPN, indicating that the possible mechanism of the preventive effective on DPN were regulating VEGF expression. |
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