Department of Hand Surgery, Wound Reconstructive Surgery, and Burn Surgery, Lishui People's Hospital, Lishui, Zhejiang 323000, China.
Department of Hand Surgery, Wound Reconstructive Surgery, and Burn Surgery, Lishui People's Hospital, Lishui, Zhejiang 323000, China.
Tissue Cell. 2024 Oct;90:102483. doi: 10.1016/j.tice.2024.102483. Epub 2024 Jul 19.
Wound therapies utilizing gene delivery to the skin offer considerable promise owing to their localized treatment benefits and straightforward application. This study investigated the impact of skin electroporation of CYP1A1 shRNA lentiviral particles on diabetic wound healing in a streptozotocin (STZ)-induced rat model.
Male Sprague Dawley (SD) rats were made diabetic by injecting STZ and subsequently creating foot skin wounds. The rats were randomly divided into four groups: normal, diabetic foot ulcers (DFU), DFU + control shRNA (electroporation of control shRNA lentiviral particles), and DFU + CYP1A1 shRNA (electroporation of CYP1A1 shRNA lentiviral particles). Wound healing progress was monitored at multiple time points (0, 1, 3, 5, 7, 10, 14 days). On day 14, wound tissue specimens were collected for histological examination. Wound samples collected at days 7 and 14 were used for gene expression analysis via qRT-PCR, assessment of CYP1A1 protein levels using western blotting, and evaluation of oxidative stress markers.
Treatment with CYP1A1 shRNA significantly enhanced diabetic wound healing rates compared to untreated controls over the observation period. Histological analysis revealed improved wound characteristics in the CYP1A1 shRNA-treated group, including enhanced epithelial regeneration, reduced inflammation, and increased collagen deposition, indicative of improved tissue repair. Furthermore, suppression of CYP1A1 corresponded with decreased expression levels of pro-inflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and diminished oxidative stress markers (malondialdehyde, superoxide dismutase) within wound tissues.
Targeted suppression of CYP1A1 represents a promising therapeutic strategy to enhance diabetic wound healing by modulating inflammation and oxidative stress.
由于基因传递到皮肤的伤口治疗具有局部治疗益处和简单的应用，因此具有很大的应用前景。本研究通过链脲佐菌素（STZ）诱导的大鼠模型，研究了 CYP1A1 shRNA 慢病毒颗粒皮肤电穿孔对糖尿病创面愈合的影响。
通过注射 STZ 使雄性 Sprague Dawley（SD）大鼠产生糖尿病，然后创建足部皮肤伤口。大鼠随机分为四组：正常组、糖尿病足溃疡（DFU）组、DFU+对照 shRNA（电穿孔对照 shRNA 慢病毒颗粒）组和 DFU+CYP1A1 shRNA（电穿孔 CYP1A1 shRNA 慢病毒颗粒）组。在多个时间点（0、1、3、5、7、10、14 天）监测伤口愈合进展。第 14 天，采集伤口组织标本进行组织学检查。第 7 天和第 14 天收集的伤口样本用于 qRT-PCR 进行基因表达分析、Western 印迹法评估 CYP1A1 蛋白水平以及评估氧化应激标志物。
在观察期间，与未治疗的对照组相比，用 CYP1A1 shRNA 治疗显着提高了糖尿病创面的愈合率。组织学分析显示，CYP1A1 shRNA 治疗组的伤口特征得到改善，包括增强的上皮再生、减少的炎症和增加的胶原蛋白沉积，表明组织修复得到改善。此外，CYP1A1 的抑制与伤口组织中促炎细胞因子（白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6）和氧化应激标志物（丙二醛、超氧化物歧化酶）表达水平降低相关。
通过调节炎症和氧化应激，靶向抑制 CYP1A1 是增强糖尿病创面愈合的一种很有前途的治疗策略。
