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

Abstract

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

CLC Number:

R641

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.

Figures/Tables 14

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References 33

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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

Ferulic acid improves delayed wound healing caused by arsenic poisoning by inhibiting NF-κB signaling

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时间	Control组	NaAsO₂组	NaAsO₂+FA组	FA组	F值
24 h	1.01 ± 0.12	0.72 ± 0.04^*	0.86 ± 0.08	1.07 ± 0.23	13.35
48 h	1.29 ± 0.07	0.73 ± 0.03^*	0.97 ± 0.05^#	1.28 ± 0.06	118.80
72 h	1.50 ± 0.10	0.84 ± 0.03^*	1.18 ± 0.04^#	1.47 ± 0.04	102.10

炎性因子	Control组	NaAsO₂组	NaAsO₂+FA组	FA组	F值
IL-1β	0.99 ± 0.13	3.36 ± 0.31^*	2.08 ± 0.24^#	0.93 ± 0.14	138.8
IL-6	0.98 ± 0.12	2.91 ± 0.28^*	1.99 ± 0.17^#	0.91 ± 0.09	142.6
TNF-α	1.03 ± 0.16	2.83 ± 0.19^*	1.92 ± 0.18^#	1.00 ± 0.17	123.2
IFN-γ	0.97 ± 0.09	4.01 ± 0.33^*	2.76 ± 0.29^#	1.06 ± 0.17	183.7

紧密连接蛋白	Control组	NaAsO₂组	NaAsO₂+FA组	FA组	F值	P值
Claudin-1	1.03 ± 0.15	0.24 ± 0.07^*	0.52 ± 0.10^#	1.12 ± 0.13	56.35	0.000 1
Occludin	0.95 ± 0.14	0.20 ± 0.05^*	0.43 ± 0.04^#	0.99 ± 0.17	91.03	0.000 1

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