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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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| 篇名： | 熊果酸对变应性接触性皮炎模型大鼠的改善作用及机制 |
| TITLE： | Improvement effect and mechanism of ursolic acid on allergic contact dermatitis model rats |
| 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，50mg/kg）、熊果酸高剂量组（UA-H组，100mg/kg）和熊果酸高剂量+Notch1激活剂组（UA-H+Jagged1组，100mg/kg熊果酸+50ng/kgJagged1），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14d。末次给药后24h，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。 |
| 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. |
| 期刊： | 2025年第36卷第20期 |
| 作者： | 杨阳；张莹；刘甜；彭蕾蕾；潘芸 |
| AUTHORS： | YANG Yang，ZHANG Ying，LIU Tian，PENG Leilei，PAN Yun |
| 关键字： | 熊果酸；变应性接触性皮炎；Notch1/Hes1信号通路 |
| KEYWORDS： | ursolic acid； allergic contact dermatitis； Notch1/Hes1 signaling pathway |
| 阅读数： | 1 次 |
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