止痛消炎膏抑制RAGE通路善表皮屏障治疗慢性湿疹*

作者：王星星，景慧玲，郭佑祯，史敏娜，冯璟璟

单位：西安市中医医院，陕西 西安 710021

引用：引用：王星星，景慧玲，郭佑祯，史敏娜，冯璟璟.止痛消炎膏抑制RAGE通路改善表皮屏障治疗慢性湿疹[J].中医药导报,2026,32(3):38-43,81.

DOI：10.13862/j.cn43-1446/r.2026.03.007

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摘要：目的：探讨止痛消炎膏通过调控晚期糖基化终末产物受体（RAGE）信号通路治疗慢性湿疹的作用机制。方法：将40只Balb/c雄性小鼠随机分为正常组、模型组、止痛消炎膏组、阳性药组，每组10只，用5%的2,4-二硝基氯苯（DNCB）50 μL以及0.1% DNCB 100 μL刺激造模，连续4周，实验结束后处死。将人表皮角质形成细胞（HaCaT）分成：空白组（正常培养的HaCaT细胞）；模型组[肿瘤坏死因子-α（TNF-α）/γ干扰素（IFN-γ）诱导的炎症模型细胞]；止痛消炎膏低浓度组：造模成功后，浓度为0.5 mg/mL干预细胞24 h；止痛消炎膏中浓度组：造模成功后，浓度为1.0 mg/mL干预细胞24 h；止痛消炎膏高浓度组：造模成功后，浓度为2.0 mg/mL干预细胞24 h。干预结束后观察止痛消炎膏对慢性湿疹模型病理影响；采用实时荧光定量逆转录-聚合酶链反应（qRT-PCR）检测JUN蛋白（Jun） mRNA、RAGE mRNA、TNF-α mRNA、IFN-γ mRNA、白细胞介素-13（IL-13） mRNA、早期生长反应因子1（Egr1） mRNA、核因子κB（NF-κB） mRNA含量的改变；Western blotting检测小鼠组织和细胞中TNF-α、IFN-γ、IL-13、Egr1、Jun、RAGE、NF-κB p65蛋白含量的改变。结果：止痛消炎膏组和阳性药组小鼠表皮厚度减小，棘层变薄，水肿减轻，真皮层炎症细胞浸润减轻。在细胞水平方面：模型组中TNF-α mRNA、IL-13 mRNA、Egr1 mRNA、NF-κB p65 mRNA及蛋白表达水平，RAGE蛋白表达水平均高于正常组（P＜0.01）；Jun mRNA、IFN-γ mRNA及蛋白表达水平均低于正常组（P＜0.01）；止痛消炎膏高浓度组TNF-α mRNA、IL-13 mRNA、Egr1 mRNA、NF-κB p65 mRNA及蛋白表达水平，RAGE蛋白表达水平均低于模型组（P＜0.05），IFN-γ mRNA、Jun mRNA及蛋白表达水平均高于模型组（P＜0.05）。在动物水平研究中：模型组小鼠皮损组织中TNF-α mRNA、IL-13 mRNA、Egr1 mRNA、NF-κB p65 mRNA及蛋白表达水平，RAGE蛋白表达水平均高于正常组（P＜0.01），Jun mRNA、IFN-γ mRNA及蛋白表达水平均低于正常组（P＜0.05）；止痛消炎膏组小鼠皮损组织中TNF-α mRNA、IL-13 mRNA、Egr1 mRNA、NF-κB p65 mRNA及蛋白表达水平，RAGE蛋白表达水平均低于模型组（P＜0.05），Jun mRNA、IFN-γ mRNA及蛋白表达水平均高于模型组（P＜0.05）。结论：止痛消炎膏通过抑制RAGE信号通路改善Jun，从而减轻慢性湿疹的症状。

关键词：慢性湿疹；止痛消炎膏；晚期糖基化终末产物受体；小鼠；HaCaT细胞

Abstract：

Objective: To investigate the mechanism of Zhitong Xiaoyan Ointment in the treatment of chronic eczema by regulating the receptor for advanced glycation end products (RAGE) signaling pathway. Methods: Forty male Balb/c mice were randomly divided into a normal group, a model group, a Zhitong Xiaoyan Ointment group, and a positive drug group, with 10 mice in each group. The model was established by topical application of 50 μL of 5% 2,4-dinitrochlorobenzene (DNCB) followed by 100 μL of 0.1% DNCB for 4 consecutive weeks. All mice were sacrificed after the experiment. Human epidermal keratinocytes (HaCaT) were divided into a blank group (normally cultured HaCaT cells), a model group [inflammatory model cells induced by tumor necrosis factor-alpha (TNF-α)/interferon-gamma (IFN-γ)], a Zhitong Xiaoyan Ointment low-concentration group (cells treated with 0.5 mg/mL of the ointment for 24 h after successful modeling), a Zhitong Xiaoyan Ointment medium-concentration group (cells treated with 1.0 mg/mL of the ointment for 24 h after successful modeling), and a Zhitong Xiaoyan Ointment high-concentration group (cells treated with 2.0 mg/mL of the ointment for 24 h after successful modeling). After the intervention, the pathological effects of Zhitong Xiaoyan Ointment on the chronic eczema model were observed. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of Jun mRNA, RAGE mRNA, TNF-α mRNA, IFN-γ mRNA, interleukin-13 (IL-13) mRNA, early growth response factor 1 (Egr1) mRNA, and nuclear factor-κB (NF-κB) mRNA. Western blotting was used to detect the protein expression levels of TNF-α, IFN-γ, IL-13, Egr1, Jun, RAGE, and NF-κB p65 in mouse tissues and cells. Results: In the Zhitong Xiaoyan Ointment group and the positive drug group, the epidermal thickness of mice was reduced, the stratum spinosum became thinner, edema was alleviated, and inflammatory cell infiltration in the dermis was diminished. At the cellular level, the mRNA and protein levels of TNF-α, IL-13, Egr1, NF-κB p65, and the protein level of RAGE in the model group were significantly higher than those in the blank group (P<0.01), while the mRNA and protein levels of Jun and IFN-γ were lower than those in the blank group (P<0.01). In the Zhitong Xiaoyan Ointment high-concentration group, the mRNA and protein expression levels of TNF-α, IL-13, Egr1 and NF-κB p65, the protein level of RAGE were lower than those in the model group (P<0.05), while the mRNA and protein expression levels of IFN-γ and Jun were higher than those in the model group (P<0.05). In the animal study, the mRNA and protein expression levels of TNF-α, IL-13, Egr1, and NF-κB p65, and the protein level of RAGE in the skin lesions of the model group were higher than those in the normal group (P<0.01), while the mRNA and protein levels of Jun and IFN-γ were lower than those in the normal group (P<0.05). In the Zhitong Xiaoyan Ointment group, the mRNA and protein levels of TNF-α, IL-13, Egr1, and NF-κB p65, and the RAGE protein level in the skin lesions were lower than those in the model group (P<0.05), while the mRNA and protein levels of Jun and IFN-γ were higher than those in the model group (P<0.05). Conclusion: Zhitong Xiaoyan Ointment can alleviate the symptoms of chronic eczema, and its mechanism may be related to inhibiting the RAGE signaling pathway to improve Jun. Conclusion: Zhitong Xiaoyan Ointment can alleviate chronic eczema symptoms by inhibiting the RAGE signaling pathway to improve Jun.

Key words：chronic eczema; Zhitong Xiaoyan Ointment; RAGE; mice; HaCaT cells

发布时间：2026-03-28

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