SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamilnadu, India.
Department of Biotechnology, School of Bio-engineering, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamilnadu, India.
Free Radic Biol Med. 2019 Jul;138:53-62. doi: 10.1016/j.freeradbiomed.2019.04.031. Epub 2019 Apr 26.
Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic foot ulcer (DFU) treatment due to its antimicrobial effect, increased angiogenesis and enhanced collagen synthesis. The molecular mechanism underlying HBO therapy particularly the involvement of Nrf2 in the wound healing process was investigated in the present study. In addition, we have studied the levels of angiogenic markers in ulcer tissues and their correlation with Nrf2 during HBO therapy compared with standard therapy (Non-HBO) for DFU. A total of 32 Patients were recruited and randomized to standard wound care procedure alone (n = 17) or HBO therapy in combination with standard wound care procedure (n = 15) for 20 days. Our results showed that the tissue levels of Nrf2 along with its downstream targets were significantly increased in patients who underwent HBO therapy when compared to Non-HBO therapy. Further, HBO therapy induced angiogenesis as assessed by increased levels of angiogenesis markers such as EGF, VEGF, PDGF, FGF-2 and CXCL10 in the tissue samples. The expressions of eNOS and nitrite concentrations were also significantly increased in HBO therapy when compared to Non-HBO therapy subjects. Moreover, HBO therapy sensitises the macrophages to release FGF-2 and EGF thereby promotes angiogenesis. Further, it increased the levels of neutrophil attractant CXCL-8 thereby promotes the release of chemokine CCL2, a well-known mediator of neovascularization. The Pearson correlation showed that Nrf2 has a positive correlation with EGF, VEGF and PDGF. In conclusion, the findings of the present study suggest that HBO therapy promotes wound healing by increasing oxygen supply and distribution to damaged tissues, stimulating angiogenesis, decreasing inflammation, and increasing the nitrite levels. Increased levels of Nrf2 transiently regulate the expression of angiogenic genes in wound biopsies, which may result in accelerated healing of chronic wounds.
高压氧（HBO）治疗因其抗菌作用、增加血管生成和增强胶原蛋白合成而被证明对糖尿病足溃疡（DFU）的治疗非常成功。本研究旨在探讨 HBO 治疗的分子机制，特别是 Nrf2 在伤口愈合过程中的作用。此外，我们还研究了溃疡组织中血管生成标志物的水平及其与 HBO 治疗期间 Nrf2 的相关性，与 DFU 的标准治疗（非 HBO）进行比较。共招募了 32 名患者，并随机分为仅接受标准伤口护理程序（n=17）或 HBO 治疗联合标准伤口护理程序（n=15）治疗 20 天。我们的结果表明，与非 HBO 治疗相比，接受 HBO 治疗的患者组织中 Nrf2 及其下游靶标水平显著升高。此外，HBO 治疗诱导了血管生成，如组织样本中血管生成标志物如 EGF、VEGF、PDGF、FGF-2 和 CXCL10 的水平增加。与非 HBO 治疗组相比，eNOS 的表达和亚硝酸盐浓度也显著增加。此外，HBO 治疗使巨噬细胞敏感地释放 FGF-2 和 EGF，从而促进血管生成。此外，它增加了中性粒细胞趋化因子 CXCL-8 的水平，从而促进趋化因子 CCL2 的释放，CCL2 是血管新生的一种已知介质。Pearson 相关性分析表明，Nrf2 与 EGF、VEGF 和 PDGF 呈正相关。总之，本研究的结果表明，HBO 治疗通过增加氧气供应和分布到受损组织、刺激血管生成、减少炎症和增加亚硝酸盐水平来促进伤口愈合。Nrf2 水平的升高暂时调节了伤口活检中血管生成基因的表达，这可能导致慢性伤口的愈合加速。
