目的 研究三黄凝胶对痤疮模型大鼠髓样分化因子（MyD88）/白细胞介素 1 受体相关激酶 1（IRAK1）/肿瘤 坏死因子受体相关因子 6（TRAF6）/核转录因子 κB（NF-κB）信号通路及下游相关因子表达的影响，探讨其治疗 痤疮的作用机制。方法 将 60 只 Wistar 雄性大鼠随机分为空白组、模型组、阳性对照组（盐酸克林霉素凝胶， 10 g·kg-1 ）及三黄凝胶高、中、低剂量组（生药量 280、140、70 g·kg-1 ），每组 10 只。采用右耳耳廓开口处涂抹 油酸+皮下注射痤疮丙酸杆菌诱导耳廓复合痤疮大鼠模型，大鼠耳廓皮损面积为 1 cm2 。模型复制成功后给药组 均每次涂抹 0.25 g 相应药物，每日 1 次，连续给药 28 d。观察各组大鼠耳廓皮损变化；采用 HE 染色法观察耳 廓组织病理变化；RT-qPCR 法检测耳廓组织中 MyD88、TRAF6、NF-κB p65 mRNA 表达；Western Blot 法检测 耳廓组织中 MyD88、IRAK1、TRAF6、NF-κB p65、白细胞介素 1β（IL-1β）、白细胞介素 18（IL-18）蛋白表达 水平；免疫组化法检测耳廓组织中 NOD 样受体蛋白 3（NLRP3）、半胱氨酸天冬氨酸蛋白酶 1（Caspase-1）、衔 接分子（ASC）蛋白表达水平。结果 与空白组比较，模型组大鼠耳廓皮肤外观可见明显丘疹、脓疱、囊肿，伴 有角质层及表皮明显增厚，大量炎性细胞浸润，毛囊口大量角化物等病理改变；耳廓组织中 MyD88、TRAF6、 NF-κB p65 mRNA 表达水平均显著升高（P＜0.01），MyD88、IRAK1、TRAF6、NF-κB p65、IL-1β、IL-18、 NLRP3、ASC、Caspase-1 蛋白表达水平均显著升高（P＜0.01）。与模型组比较，各给药组大鼠耳廓丘疹脓疱及 角质层增厚、炎性细胞浸润情况明显改善，其中以三黄凝胶高剂量组效果更佳；各给药组大鼠耳廓组织中 MyD88、 TRAF6、 NF- κB p65 mRNA 表 达 水 平 均 显 著 降 低（P＜0.01）， MyD88、 IRAK1、 IL-1β、 IL-18、 Caspase-1 蛋白表达水平显著降低（P＜0.05，P＜0.01）；阳性对照组及三黄凝胶高剂量组大鼠耳廓组织中 TRAF6、NF-κB p65、ASC 蛋白表达水平显著降低（P＜0.01）；阳性对照组及三黄凝胶中、高剂量组大鼠耳廓 组织中 NLRP3 表达量显著降低（P＜0.05，P＜0.01）。结论 三黄凝胶可以明显改善痤疮模型大鼠耳廓组织丘 疹、脓疱等轻中度痤疮皮损，减轻炎症损伤，其作用机制可能与调控 MyD88/IRAK1/TRAF6/NF-κB 信号通路及 下游 NLRP3 炎性小体、IL-1β、IL-18 表达，改善皮肤免疫炎症反应有关。

Objective To investigate the effects of Sanhuang Gel on the myeloid differentiation factor 88（MyD88）/ interleukin-1 receptor-associated kinase 1 （IRAK1）/tumor necrosis factor receptor-associated factor 6 （TRAF6）/ nuclear factor- κB （NF- κB） signaling pathway and the expression of downstream factors in acne model rats，and to explore its mechanism in treating acne. Methods Sixty male Wistar rats were randomly divided into a blank group，a model group，a positive control group （Clindamycin Hydrochloride Gel，10 g·kg-1 ），and high-，medium-，and lowdose Sanhuang Gel groups （crude drug doses of 280，140，and 70 g·kg-1 ，respectively），with 10 rats in each group. A composite acne model was induced by applying oleic acid and injecting Propionibacterium acnes at the opening of the right ear auricle，with a lesion area of 1 cm2 . After successful model establishment，the treatment groups were topically administered 0.25 g of the corresponding drug once daily for 28 days. Changes in auricular lesions were observed. Pathological changes in auricular tissues were examined using HE staining. RT-qPCR was used to detect the mRNA expressions of MyD88， TRAF6， and NF- κB in auricular tissues. Western Blot was used to measure the protein expression levels of MyD88，IRAK1，TRAF6，NF-κB p65，interleukin-1β（IL-1β），and interleukin-18（IL-18） in auricular tissues. Immunohistochemistry was used to detect the protein expression levels of NOD-like receptor protein 3（NLRP3）， cysteine-dependent aspartate-specific protease 1（Caspase-1）， and apoptosis-associated speck-like protein containing a CARD （ASC） in auricular tissues. Results Compared with the blank group， the model group showed significant papules， pustules， and cysts on the auricular skin， accompanied by thickening of the stratum corneum and epidermis，massive inflammatory cell infiltration， and a large amount of keratin in hair follicles. The mRNA expression levels of MyD88，TRAF6，and NF-κB p65 in auricular tissues were significantly increased （P＜ 0.01），and the protein expression levels of MyD88，IRAK1，TRAF6，NF-κB p65，IL-1β，IL-18，NLRP3，ASC， and Caspase-1 were significantly elevated （P＜0.01）. Compared with the model group，all treatment groups improved papules，pustules，thickening of the stratum corneum，and inflammatory cell infiltration in the auricular tissues，with the high-dose group showing the best effect. The mRNA expression levels of MyD88，TRAF6，and NF- κB p65 in auricular tissues were significantly reduced in all treatment groups （P＜0.01）， and the protein expression levels of MyD88， IRAK1， IL-1β， IL-18， and Caspase-1 were significantly decreased （P＜0.05， P＜0.01）. The protein expression levels of TRAF6， NF- κB p65， and ASC in auricular tissues were significantly reduced in the positive control group and high-dose group （P＜0.01）. The expression of NLRP3 in auricular tissues was significantly reduced in the positive control group and medium- and high-dose Sanhuang Gel groups （P＜0.05， P＜0.01）. Conclusion Sanhuang Gel can significantly improve papules，pustules，and other mild to moderate acne lesions in the auricular tissues of acne model rats，alleviating inflammatory damage. Its mechanism may be related to regulating the MyD88/ IRAK1/TRAF6/NF- κB signaling pathway and downstream NLRP3 inflammasome， IL-1β， and IL-18 expression， thereby improving skin immune-inflammatory responses.

R285.5

甘肃省高等学校科技成果转化项目（2017D-17）；甘肃省教育厅科技创新项目（2023A-079）；甘肃省高校产业支撑计划项目（2025CYZC- 046）。