Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China.
Int Wound J. 2020 Jun;17(3):851-863. doi: 10.1111/iwj.13341. Epub 2020 Mar 13.
Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high-voltage and high-frequency power supply. Eight-week-old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low-dose group), and 180s' CAP (high-dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound-healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low-dose group and high-dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL-6, tumour necrosis factor-α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor-β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound-healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.
冷等离体等离子体（CAP）是工作气体产生的各种化学活性物质的集合，如臭氧和一氧化氮。CAP 已被证明对组织再生和伤口愈合有影响。我们进行这项研究是为了评估 CAP 作为一种新型糖尿病伤口治疗方法的疗效和安全性，体外和体内。等离子体由电离氦气组成，由高压和高频电源产生。8 周龄雄性 db/db 小鼠和 C57BL 小鼠接受氦气（对照组）、90 秒 CAP（低剂量组）和 180 秒 CAP（高剂量组）治疗。治疗并观察 2 周。采集伤口周围皮肤样本和血液样本。我们的体外分析包括使用人永生化人表皮细胞 HaCaT 进行划痕伤口愈合试验。经过 14 天的治疗，CAP 可以明显促进糖尿病伤口愈合。低剂量组和高剂量组的伤口闭合率明显高于对照组。同时，与对照组相比，低剂量组和高剂量组的白细胞介素 6、肿瘤坏死因子-α、诱导型一氧化氮合酶和超氧化物歧化酶的蛋白表达明显降低，而低剂量组和高剂量组的血管内皮生长因子和转化生长因子-β的蛋白表达明显增加（均 P <.05）；这些数据与 mRNA 水平的变化很好地一致（均 P <.05）。在体外，划痕伤口愈合试验表明，等离子体处理可以在暴露 3 分钟内有效地确保愈合（均 P <.05）。此外，在 CAP 组和对照组的正常皮肤组织学观察和血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血尿素氮、肌酐和白细胞水平方面，没有发现差异。每天 3 分钟的 CAP 治疗通过抑制炎症、减少氧化应激和增强血管生成来改善糖尿病小鼠的伤口愈合，涉及几种蛋白信号，对肝脏和肾脏是安全的。
