| Aims Diabetic foot is one of the most common and severe complications of diabetes.And diabetic peripheral neuropathy(DPN)is critical in the development of diabetic foot.Vitamin D deficiency(VDD)was reported to be associated with neurodegenerative disease and diabetes.However the association between DPN and VDD was unclear.Cold atmospheric plasma(CAP)interacted with tissue and had potential effects on wound healing and tissue regeneration.The aim of this study is to investigate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and vivo.Methods A total of 861 patients with type 2 diabetes were recruited in this cross-sectional study.VDD was defined as serum circulating 25-hydroxyvitamin D(25(OH)D)level< 20 ng/mL.DPN was evaluated by neurological symptoms,neurological signs,neurothesiometer,and electromyogram.The plasma consists of ionized helium gas that is produced by a high-voltage(8.5kV)and high-frequency(17 kHz)power supply.Eight-week-old male db/db mice were treated with helium gas(control group),90's CAP(low-dose group)and 180's CAP(medium-dose group).Mice were treated and observed for 2 weeks.Skin samples around wound in 3,7,14 days and blood samples were collected and analyzed in three groups.Results The patients with DPN had significantly lower serum 25(OH)D concentration(15.59 ± 7.68 ng/mL)and higher prevalence of VDD(80%)than patients with signs of DPN(17.66 ± 7.50ng/mL;64.5%)and non-DPN patients(18.35 ± 6.60;61.7%)(all P < 0.01).Spearman's correlation analysis showed that serum circulating 25(OH)D level was closely associated with DPN(r = 0.121)and sings of DPN(r = 0.111)(both P <0.01).After adjusting for all potential confounders,VDD was still linked with increased risk of DPN [odds ratio(OR)2.59(1.48–4.53)](P <0.01).Logistical regression analysis further revealed that VDD was an independent risk factor for DPN(? = 0.88)(P <0.01).ROC analysis indicated that serum 25(OH)D <17.22 ng/mL hinted the signs of DPN and serum 25(OH)D <16.01ng/ml predicted the occurrence of DPN(both P <0.01).In basic research,we found that after 14 days of treatment,CAP could obviously promote diabetic wound healing because of inhibiting inflammation and enhancing angiogenesis.Wound-closure rates were significantly faster in the low-does group and high-does groups than in the control group.Meanwhile,the protein expression of IL-6,TNF-?,i NOS and SOD in two CAP groups were significantly decreased than those in control group and the protein expression of VEGF,TGF-? in two CAP groups were significantly increased compared to those in control group(all P < 0.05),these data showing a good agreement with the change in mRNA level(all P < 0.05).Additionally,there was no difference in histological observation and the level of serum ALT,AST,BUN,Cr and white blood cell among CAP groups and control group.Conclusions VDD is an independent risk factor for DPN.It hints a nearly 3-fold risk of DPN when the concentration of 25(OH)D is < 16.01 ng/mL in Chinese patients with Type 2 diabetes.Furthermore,our data suggest that the 3 min CAP treatment improves diabetic wound healing by inhibiting inflammation and enhancing angiogenesis,involving several proteins signaling.And no relevant side effects on liver and kidney were detected. |
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