Page 55 - 《中国药房》2025年20期

熊果酸对变应性接触性皮炎模型大鼠的改善作用及机制
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杨 阳 ，张 莹，刘 甜，彭蕾蕾，潘 芸（武汉市第六医院皮肤科，武汉 430015）
中图分类号 R965；R285.5 文献标志码 A 文章编号 1001-0408（2025）20-2537-05
DOI 10.6039/j.issn.1001-0408.2025.20.09

摘 要 目的 探讨熊果酸对变应性接触性皮炎（ACD）大鼠皮肤炎症的改善作用，并基于Notch1/毛状分裂增强子1（Hes1）信号通
路探索其作用机制。方法 采用2，4-二硝基氯苯涂抹的方法建立ACD模型。将建模成功的40只大鼠随机分为模型组（MC组）、
熊果酸低剂量组（UA-L组，50 mg/kg）、熊果酸高剂量组（UA-H组，100 mg/kg）和熊果酸高剂量+Notch1激活剂组（UA-H+Jagged1
组，100 mg/kg熊果酸+50 ng/kg Jagged1），每组10只；另选10只仅脱毛的正常大鼠作为正常对照组。各药物组大鼠灌胃相应剂量
熊果酸或（和）腹腔注射相应剂量Jagged1，每天1次，持续14 d。末次给药后24 h，对各组大鼠进行皮肤炎症状态观察和皮炎评分，
采用酶联免疫吸附测定法测定血清及皮肤组织中白细胞介素6（IL-6）、IL-17、IL-10水平，苏木精-伊红染色法观察其皮肤组织病理
形态，免疫组化法和免疫印迹法检测其皮肤组织中Notch1、Hes1蛋白的表达情况。结果 与MC组比较，UA-L组和UA-H组大鼠
皮炎评分均显著降低，皮肤组织炎症细胞浸润等病理损伤均有不同程度减轻，血清及皮肤组织中IL-6、IL-17水平均显著降低，IL-
10水平均显著升高，Notch1、Hes1蛋白的表达均显著下调（P＜0.05），且UA-H 组上述指标的改善更明显（P＜0.05）；Jagged1可显
著减弱高剂量熊果酸对上述指标的改善作用（P＜0.05）。结论 熊果酸可能通过抑制Notch1/Hes1信号通路来减弱促炎性细胞因
子表达并增强抗炎细胞因子表达，进而改善ACD大鼠的皮炎症状。
关键词 熊果酸；变应性接触性皮炎；Notch1/Hes1信号通路

Improvement effect and mechanism of ursolic acid on allergic contact dermatitis model rats
YANG Yang， ZHANG Ying， LIU Tian， PENG Leilei， PAN Yun（Dept. of Dermatology， Wuhan Sixth Hospital，
Wuhan 430015， China）
ABSTRACT OBJECTIVE To investigate the ameliorative effect of ursolic acid on skin inflammation in rats with allergic contact
dermatitis （ACD）， and explore its mechanism of action based on the Notch1/hairy and enhancer of split 1 （Hes1） signaling
pathway. METHODS The ACD model was established by skin application of 2， 4-dinitrochlorobenzene. Forty successfully modeled
rats were randomly divided into model control group （MC group）， ursolic acid low-dose group （UA-L group， 50 mg/kg）， ursolic
acid high-dose group （UA-H group， 100 mg/kg）， and ursolic acid high-dose+Notch1 activator group （UA-H+Jagged1 group， 100
mg/kg ursolic acid+50 ng/kg Jagged1）， with 10 rats in each group. Another 10 rats with only hair shedding were selected as the
normal control group. Rats in the administration groups were given the corresponding dose of ursolic acid intragastrically or/and
Jagged1 by intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last treatment， the skin
inflammation status and dermatitis scores of rats in each group were detected. The levels of interleukin-6 （IL-6）， IL-17 and IL-10
in serum and skin tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the
pathological morphology of the skin tissue. Immunohistochemical staining and immunoblotting assay were used to detect the protein
expressions of Notch1 and Hes1 in skin tissues. RESULTS Compared with the MC group， both the UA-L group and UA-H group
exhibited significantly lower dermatitis scores， along with varying degrees of reduction in histopathological skin damage such as
inflammatory cell infiltration. Additionally， the levels of IL-6 and IL-17 in serum and skin tissues were markedly decreased， while
the levels of IL-10 were significantly increased in both groups； protein expressions of Notch1 and Hes1 were decreased significantly
（P＜0.05）， and the improvements in the aforementioned indicators were more significant in the UA-H group （P＜0.05）. Jagged1
could significantly weaken the improvement effects of UA-H on the above indicators （P＜0.05）. CONCLUSIONS Ursolic acid
may attenuate the expression of pro-inflammatory cytokines and enhance the expression of anti-inflammatory factors by blocking
Notch1/Hes1 signaling pathway， thereby improving dermatitis symptoms in ACD rats.
KEYWORDS ursolic acid； allergic contact dermatitis； Notch1/Hes1 signaling pathway

变 应 性 接 触 性 皮 炎（allergic contact dermatitis， 细胞异常激活导致的免疫炎症反应是诱发ACD的主要
ACD）是一种常见的炎症性皮肤病。研究指出，T 淋巴 机制，白细胞介素6（interleukin-6，IL-6）、IL-10等炎症因
子在此过程中发挥了关键的调控作用，故抗炎是临床治
Δ 基金项目 武汉市中医药科研项目（No.WZ22C11） 疗 ACD 的有效方法 。熊果酸是一种天然三萜羧酸化
[1]
＊第一作者 主治医师，硕士。研究方向：过敏性皮肤病、痤疮、面
合物，具有抗炎活性，可通过减少活性氧、促炎性细胞因
部年轻化及色素性疾病。E-mail：vjsv6pu@163.com [2]
# 通信作者 主治医师，硕士。研究方向：湿疹、荨麻疹、中重度痤 子生成来抑制免疫炎症 。已有研究报道，熊果酸能够
疮、瘢痕、天疱疮等。E-mail：y5ee32d0@163.com 通过改善炎症反应和氧化应激来减轻特应性皮炎小鼠

中国药房 2025年第36卷第20期 China Pharmacy 2025 Vol. 36 No. 20 · 2537 ·