文献类型：期刊文献

中文题名：三黄凝胶对痤疮模型大鼠MyD88/IRAK1/TRAF6/NF-κB信号通路及下游相关因子的影响

英文题名：Effects of Sanhuang Gel on the MyD88/IRAK1/TRAF6/NF-κB Signaling Pathway and Downstream-Related Factors in Acne Model Rats

作者：杜雪洋[1];董小平[1];牛凡琪[1];郭斐斐[1];杨鹏斐[1];金彩云[1];王思农[1]

第一作者：杜雪洋

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：36

期号：5

起止页码：666

中文期刊名：中药新药与临床药理

外文期刊名：Traditional Chinese Drug Research and Clinical Pharmacology

收录：;北大核心:【北大核心2023】；

基金：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)。

语种：中文

中文关键词：三黄凝胶;痤疮;MyD88/IRAK1/TRAF6/NF-κB信号通路;NLRP3炎性小体;炎症因子;大鼠

外文关键词：Sanhuang Gel;acne;MyD88/IRAK1/TRAF6/NF-κB signaling pathway;NLRP3 inflammasome;inflammatory factors;rats

摘要：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 cm^(2)。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 cm^(2).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.