阿魏酸通过抑制NF-κB信号改善砷中毒导致的伤口愈合延迟

doi:10.3969/j.issn.1006-5725.2026.13.021

摘要/Abstract

摘要：

目的在砷中毒小鼠皮肤伤口模型中，探讨阿魏酸（ferulic acid， FA）在砷中毒诱导的小鼠伤口愈合延迟中的治疗作用以及机制研究。方法（1）雄性C57BL/6小鼠喂以含NaAsO₂的饮水3个月以建立砷中毒模型。（2）在正常小鼠与砷中毒小鼠背部建立皮肤全层缺损，并将生理盐水或FA溶液涂在小鼠背部伤口处，分为对照（Control）组、FA组、砷中毒（NaAsO₂）组、NaAsO₂+FA组。通过拍照采集伤口图像、收集伤口组织进行HE染色与MASSON染色观察伤口愈合程度，采用Real-time PCR检测炎性因子以及采用Western blot检测紧密连接蛋白（Claudin-1、Occludin）、核因子κB（nuclear factor kappa-B， NF-κB）通路关键蛋白（p65、P-p65）的表达。（3）人脐静脉内皮细胞（human umbilical vein endothelial cells， HUVECs）分为对照组、NaAsO₂刺激组、NaAsO₂+FA组及FA单独处理组，验证NaAsO₂对HUVEC细胞增殖和迁移能力、炎性因子、紧密连接蛋白的表达以及NF-κB通路的影响。结果（1）与对照组相比，NaAsO₂组小鼠伤口愈合速度明显减慢（P 0.05），伤口组织中胶原纤维及紧密连接蛋白的表达降低（P 0.05），炎性因子表达升高（P 0.05），NF-κB通路被激活（P 0.05）；NaAsO₂+FA组与NaAsO₂组相比，伤口愈合速度加快（P 0.05），胶原纤维及紧密连接蛋白的表达升高（P 0.05），炎性因子表达降低（P 0.05），NF-κB通路被抑制（P 0.05）。（2）在HUVEC细胞中，NaAsO₂刺激能够抑制细胞的增殖和迁移（P 0.05），下调紧密连接蛋白的表达（P 0.05），促进炎性因子的表达并激活NF-κB信号通路（P 0.05）。FA联合干预则可显著逆转由NaAsO₂所引起的上述不良效应结论（P 0.05）。结论 FA可通过抑制NF-κB信号抑制炎症反应，并上调紧密连接蛋白的表达，改善砷中毒诱导的伤口愈合延迟。

关键词: 砷中毒, 阿魏酸, 伤口愈合延迟, 紧密连接, NF-κB通路, 炎症反应, 人脐静脉内皮细胞

Abstract:

Objective To investigate the therapeutic effect and the underlying mechanism of ferulic acid （FA） on the delayed wound healing induced by arsenic poisoning in a mouse skin wound model. Methods （1） Male C57BL/6 mice were administered drinking water containing NaAsO₂ for 3 months to establish an arsenic poisoning model. （2） Full-thickness skin defects were created on the backs of normal and arsenic-poisoned mice. Subsequently， normal saline or FA solution was topically applied. The mice were divided into four groups： the control group， the FA group， the NaAsO₂ group， and the NaAsO₂+FA group. Wound healing was evaluated through photographic monitoring. Wound tissues were collected for HE staining and Masson staining to assess the degree of healing. Inflammatory factors were detected by Real-time PCR， and the expression levels of tight junction proteins （Claudin-1 and Occludin） as well as key proteins of the nuclear factor κB （NF-κB） pathway （p65 and P-p65） were measured by Western blot. （3） Human umbilical vein endothelial cells （HUVECs） were divided into four groups： the control group， the NaAsO₂ group， the NaAsO₂+FA group， and the FA group. The study aimed to verify the effects of NaAsO? on the proliferation and migration capabilities of HUVECs， as well as on the expression of inflammatory factors， tight junction proteins， and the NF-κB pathway. Results （1） When compared to the control group， the NaAsO? group in mice demonstrated significantly slower wound healing （P 0.05）. Additionally， there was a decrease in the expression of collagen fibers and tight-junction proteins in the wound tissues （P 0.05）， an increase in the expression of inflammatory factors （P 0.05）， and activation of the NF-κB pathway （P 0.05）. In contrast to the NaAsO? group， the NaAsO?+FA group showed accelerated wound healing （P 0.05）， an elevation in the expression of collagen fibers and tight-junction proteins （P 0.05）， a reduction in the expression of inflammatory factors （P 0.05）， and inhibition of the NF-κB pathway （P 0.05）. （2） In HUVEC cells， stimulation with NaAsO? significantly inhibited cell proliferation and migration （P 0.05）， down-regulated the expression of tight-junction proteins （P 0.05）， promoted the expression of inflammatory factors， and activated the NF-κB signaling pathway （P 0.05）. The combined intervention with FA could significantly reverse the adverse effects induced by NaAsO? （P 0.05）. Conclusion FA can inhibit the inflammatory response by suppressing the NF-κB signaling pathway and upregulate the expression of tight junction proteins， which in turn improves the delayed wound healing caused by arsenic poisoning.

Key words: arsenic poisoning, ferulic acid, delayed wound healing, tight junctions, NF-κB pathway, inflammatory response, human umbilical vein endothelial cells

中图分类号:

R641

李玉秀,杨喆,张振奋,徐彬桅,洪艳. 阿魏酸通过抑制NF-κB信号改善砷中毒导致的伤口愈合延迟[J]. 实用医学杂志, 2026, 42(13): 2444-2453.

Yuxiu LI,Zhe YANG,Zhenfen ZHANG,Binwei XU,Yan HONG. Ferulic acid improves delayed wound healing caused by arsenic poisoning by inhibiting NF-κB signaling[J]. The Journal of Practical Medicine, 2026, 42(13): 2444-2453.

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基因	上游引物（5′→3′）	下游引物（5′→3′）
GAPDH	GCAAGTTCAACGGCACAG	GCCAGTAGACTCCACGACAT
IL-1β	GAGCCTGTGTTTCCTCCTTG	CAAGTGCAAGGCTATGACCA
IL-6	CTCCCAACAGACCTGTCTATAC	CCATTGCACAACTCTTTTCTCA
TNF-α	CCAGTGTGGGAAGCTGTCTT	AAGCAAAAGAGGAGGCAACA
IFN-γ	CAGCAACAGCAAGGCGAAAAAGG	TTTCCGCTTCCTGAGGCTGGAT

时间	Control组	NaAsO₂组	FA组	NaAsO₂+FA组	F值	P值
第3天	31.15 ± 5.18	2.80 ± 2.01^*	28.85 ± 2.99	19.96 ± 4.75^#	63.73	0.000 1
第8天	76.16 ± 3.90	35.24 ± 4.78^*	71.38 ± 4.77	51.91 ± 6.82^#	79.24	0.000 1
第13天	100.00 ± 0.00	80.34 ± 6.38^*	100.00 ± 0.00	91.79 ± 3.35^#	40.02	0.0001

指标	Control组	NaAsO₂组	FA组	NaAsO₂+FA组	F值	P值
未愈合伤口长度/cm	0.55 ± 0.15	1.19 ± 0.13^*	0.61 ± 0.12	0.90 ± 0.20^#	22.10	0.000 1
伤口组织胶原蛋白占比/%	72.24 ± 6.12	39.69 ± 5.43^*	75.57 ± 5.35	57.92 ± 5.60^#	50.56	0.000 1

炎性因子	Control组	NaAsO₂组	FA组	NaAsO₂+FA组	F值
IL-1β	1.01 ± 0.15	3.47 ± 0.34^*	0.92 ± 0.22	2.14 ± 0.23^#	156.2
IL-6	1.19 ± 0.17	2.97 ± 0.21^*	0.99 ± 0.14	1.85 ± 0.21^#	150.3
TNF-α	1.01 ± 0.16	2.80 ± 0.18^*	1.09 ± 0.16	1.76 ± 0.14^#	163.5
IFN-γ	1.06 ± 0.13	3.90 ± 0.23^*	1.10 ± 0.13	2.72 ± 0.28^#	279.3

紧密连接蛋白	Control组	NaAsO₂组	FA组	NaAsO₂+FA组	F值	P值
Claudin-1	1.21 ± 0.16	0.22 ± 0.035^*	1.09 ± 0.26	0.66 ± 0.07^#	60.70	0.000 1
Occludin	1.15 ± 0.15	0.31 ± 0.04^*	0.97 ± 0.19	0.69 ± 0.08^#	49.57	0.000 1