Pharmacology Devision, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, 110 054, India.
Lasers Surg Med. 2020 Jun;52(5):424-436. doi: 10.1002/lsm.23156. Epub 2019 Sep 4.
Dysregulated inflammation is one of the major contributing factors for the prevalence of non-healing chronic wound in immunosuppressed subjects. Photobiomodulation (PBM) has emerged as a potential non-thermal, light-based therapeutic healing intervention for the treatment of impaired wounds.
STUDY DESIGN/MATERIALS AND METHODS: The present study delineates the underlying molecular mechanisms of PBM 810 nm laser-induced full-thickness cutaneous wound repair in immunosuppressed rats at continuous and pulsed wave-mode with power-density of 40 mW/cm , fluence 22.6 J/cm for 10 minutes daily for 7 post-wounding days. Molecular markers were assessed using biochemical, enzyme-linked immunosorbent assay quantification, enzyme kinetics and immunoblots analyses pertaining to inflammation, oxidative stress, cell survival, calcium signaling, and proliferation cascades.
Results distinctly revealed that pulsed 810 nm (10 Hz) PBM potentially influenced the cell survival and proliferation signaling pathway by significantly upregulated phospho-protein kinase B(phospho-Akt), phospho-extracellular-signal-regulated kinase 1 (ERK1), transient receptor potential vanilloid-3 (TRPV3), Ca , calmodulin, transforming growth factor-β1 (TGF-β1), TGF-βR3, and Na /K -ATPase pump levels. PBM treatment resulted in reduction of exaggerated inflammatory responses evident by significantly repressed levels of interleukin-1β (IL-1β), IL-6, cyclooxygenase 2 (COX-2), and substance-P receptor (SPR), as well as inhibited apoptotic cell death by decreasing p53, cytochrome C, and caspase 3 levels (P < 0.05), which, in turn, effectively augment the wound repair in immunosuppressed rats. PBM treatment also lowered 4-hydroxynoneal (HNE) adduct level and NADP/NADPH ratio and upregulated the GRP78 expression, which might culminate into reduced oxidative stress and maintained the redox homeostasis.
Taken together, these findings would be helpful in better understanding of the molecular aspects involved in pulsed 810 nm laser-mediated dermal wound healing in immunosuppressed rats through regulation of cell survival and proliferation via Ca -calmodulin, Akt, ERK, and redox signaling. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
炎症失调是导致免疫抑制患者慢性难愈性伤口流行的主要因素之一。光生物调节（PBM）作为一种潜在的非热、基于光的治疗方法，已经成为治疗受损伤口的一种方法。
研究设计/材料和方法：本研究在连续和脉冲波模式下，以 40mW/cm 的功率密度、22.6J/cm 的辐照量，每天照射 10 分钟，共照射 7 天，研究了 810nm 激光诱导免疫抑制大鼠全层皮肤伤口修复的潜在分子机制。采用生化、酶联免疫吸附定量、酶动力学和免疫印迹分析评估炎症、氧化应激、细胞存活、钙信号和增殖级联相关的分子标志物。
结果表明，脉冲 810nm（10Hz）PBM 通过显著上调磷酸蛋白激酶 B（磷酸化-Akt）、磷酸细胞外信号调节激酶 1（ERK1）、瞬时受体电位香草酸 3（TRPV3）、Ca 、钙调蛋白、转化生长因子-β1（TGF-β1）、TGF-βR3 和 Na /K -ATP 酶泵水平，显著影响细胞存活和增殖信号通路。PBM 治疗可降低过度的炎症反应，明显抑制白细胞介素-1β（IL-1β）、IL-6、环氧化酶 2（COX-2）和 P 物质受体（SPR）的水平，同时通过降低 p53、细胞色素 C 和半胱天冬酶 3 的水平抑制细胞凋亡（P<0.05），从而有效促进免疫抑制大鼠的伤口愈合。PBM 治疗还降低了 4-羟基壬烯醛（HNE）加合物水平和 NADP/NADPH 比值，并上调了 GRP78 的表达，这可能导致氧化应激降低和氧化还原平衡维持。
总之，这些发现有助于更好地理解脉冲 810nm 激光调节 Ca -钙调蛋白、Akt、ERK 和氧化还原信号通过调节细胞存活和增殖在免疫抑制大鼠皮肤伤口愈合中的分子机制。激光外科医学。© 2019 年 Wiley 期刊，公司。
