Pang Ting, Shao Yuankai, Zhou Li, Wang Zhibin, Xi Ping, Zhang Yuan, Xie Lihui, Deng Zhe
Department of Emergency Medicine, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
Department of Geriatrics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
Sci Rep. 2025 May 30;15(1):19085. doi: 10.1038/s41598-025-03086-5.
To investigate the effect of recombinant human aFGF (rhaFGF) on acute wounds in a diabetic mouse model focusing on the transition from acute inflammation to chronic inflammation. Diabetes mellitus (DM) mouse models were induced through intraperitoneal injection of streptozotocin and acute diabetic wounds were created on their hind paws. The mice were divided into four groups: Con, Con + rhaFGF, DM, and DM + rhaFGF. rhaFGF (0.08 µg/cm²) or PBS was daily administered on wound surface for 14 days. The levels of IL-6 and TNF-α in serum and tissues were measured using ELISA, and NLRP3 inflammasome components (NLRP3, ASC and caspase-1) and pro-inflammatory cytokines (IL-1β, IL-18) in tissue were detected by Western blot analysis. CCK8 assay and cell migration were used to assess the proliferation and migration ability of HUVEC, HFF, and HaCaT cells, respectively. Wound healing rates in the DM group decreased significantly, which was effectively alleviated by rhaFGF treatment for 7 days and longer durations. Notably, at day 7 after wound creation, the levels of IL-6 and TNF-α as well as the expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the DM group were significantly increased, and rhaFGF treatment substantially suppressed these changes. Moreover, when HUVEC, HFF, and HaCaT cells were exposed to high glucose and LPS condition, the proliferation and migration of these cells were significantly inhibited, and rhaFGF treatment effectively reversed this inhibition. rhaFGF could promote the healing of acute DM wounds by preventing chronicity transition of acute inflammation via reducing the release of pro-inflammatory cytokines and inhibiting the activation of NLRP3 in DM wounds.
为研究重组人酸性成纤维细胞生长因子（rhaFGF）对糖尿病小鼠模型急性伤口的影响，重点关注从急性炎症向慢性炎症的转变。通过腹腔注射链脲佐菌素诱导糖尿病（DM）小鼠模型，并在其后爪上制造急性糖尿病伤口。将小鼠分为四组：对照组（Con）、Con + rhaFGF组、糖尿病组（DM）和DM + rhaFGF组。每天在伤口表面给予rhaFGF（0.08 μg/cm²）或磷酸盐缓冲液（PBS），持续14天。采用酶联免疫吸附测定（ELISA）法检测血清和组织中白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，通过蛋白质免疫印迹分析检测组织中NLRP3炎性小体成分（NLRP3、凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1）以及促炎细胞因子（IL-1β、IL-18）。分别采用细胞计数试剂盒-8（CCK8）法和细胞迁移实验评估人脐静脉内皮细胞（HUVEC）、人包皮成纤维细胞（HFF）和人永生化角质形成细胞（HaCaT）的增殖和迁移能力。糖尿病组伤口愈合率显著降低，rhaFGF治疗7天及更长时间可有效缓解这一情况。值得注意的是，在伤口形成后第7天，糖尿病组IL-6和TNF-α水平以及NLRP3、ASC、半胱天冬酶-1、IL-1β和IL-18的表达显著增加，rhaFGF治疗可显著抑制这些变化。此外，当HUVEC、HFF和HaCaT细胞暴露于高糖和脂多糖（LPS）条件下时，这些细胞的增殖和迁移受到显著抑制，rhaFGF治疗可有效逆转这种抑制作用。rhaFGF可通过减少促炎细胞因子的释放和抑制糖尿病伤口中NLRP3的激活，防止急性炎症向慢性炎症转变，从而促进糖尿病急性伤口的愈合。
