Effects of pulsed electromagnetic fields on acute hindlimb ischemic diabetic rats in microcirculation angiogenesis

AIM: To observe the effects of pulsed electromagnetic fields (PEMF) on acute hindlimb ischemic diabetic rats in microcirculation angiogenesis. METHODS: Sixty male Sprague Dawley diabetic rats were randomly divided into experimental group (n=30）and control group (n=30) and acute hindlimb ischemia models were established in all rats. After operation, rats in the experimental group were exposed to PEMFs for 2 h each day, whereas rats in the control group were not given any treatment. Laser-Doppler perfusion measurements were used to determine the blood flow of hindlimb ischemia on postoperative days0, 7, 14 and 28, and immunohistochemical analysis of CD31 was used to evaluate the changes in angiogenesis. Levels of VEGF, FGF-2, VEGFR2, FGFR1, ERK1/2, P-ERK1/2, P38 and P-P38 levels were determined by Western blot analysis in ischemic skeletal muscle on postoperative days 7, 14 and 28. RESULTS: Perfusion ratios were significantly higher in PEMF-treated diabetic rats at days 14 and 28 compared with controls (0.64±0.02 vs.0.48±0.02, P<0.01); (0.85±0.02 vs.0.61±0.02, P<0.01). CD31 density in tissues measured by immunohistochemistry significantly increased in PEMF-treated groups on days 14 and 28 ［(677.4±15.6) vs.(495.2±25.3)/mm2, P<0.01; (837.2±25.6) vs.(619.4±19.2)/mm2, P<0.01］. Levels of FGF-2 and FGFR1 in ischemic hindlimbs significantly increased in PEMF group at all timepoints, as well as p-ERK1/2 and total ERK1/2. No significant differences were observed in VEGF, VEGFR2 and p-p38/total p38 between groups. CONCLUSION: PEMFs promote angiogenesis in diabetes by upregulation of FGF-2. As an indispensable signal pathway for FGF2-induced angiogenesis, ERK is responsible for coupling FGFR1 to multiple downstream pathways to mediate blood vessel formation. PEMFs can be used in the prevention and treatment of lower limb ischemia in diabetic patients.