三子颗粒治疗大鼠慢性湿疹模型皮损的作用机制研究  

Study on Mechanism of Sanzi Granules(三子颗粒)in Treating Skin Lesions in Rat Model of Chronic Eczema

作　　者：陈兴[1,2] 丛培玮[1] 孙巍[2] 关洪全[1] 李忻红[2] 王希子 侯殿东 田静[1,2] CHEN Xing;CONG Peiwei;SUN Wei;GUAN Hongquan;LI Xinhong;WANG Xizi;HOU Diandong;TIAN Jing(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China;Shenyang Seventh Peoples Hospital,Shenyang 110032,Liaoning,China;Huzhou University,Huzhou 313000,Zhejiang,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032 [3]沈阳市第七人民医院,辽宁沈阳110032 [4]湖州师范学院,浙江湖州313000

出　　处：《中华中医药学刊》2025年第4期26-32,I0005-I0007,共10页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81774023);辽宁省教育厅面上项目(LJKZ0896)。

摘　　要：目的应用三子颗粒治疗大鼠慢性湿疹模型,探讨其外治慢性湿疹的作用机制。方法40只SD雄性大鼠,随机分为正常组、模型组、三子颗粒组、青鹏软膏组,每组10只。以二硝基氯苯丙酮溶液制备大鼠慢性湿疹模型,模型组湿敷生理盐水,三子颗粒组湿敷三子颗粒洗剂,青鹏软膏组外用青鹏软膏。通过皮损评分评价疗效,苏木精-伊红染色法(hematoxylin-eosin staining,HE)染色观察皮肤组织形态学变化,甲苯胺蓝染色法观察皮肤组织肥大细胞数量,免疫组化技术检测皮损组织干扰素γ(interferon gamma,IFN-γ)、白介素4(interleukin-4,IL-4)的蛋白表达,Western blot法检测皮损组织中白介素17(interleukin-17,IL-17)、叉头样转录因子3(forkhead transcription factor 3,Foxp3)、磷酸化p38丝裂原活化蛋白激酶(phosphorylated-p38 mitogen activated protein kinase,p-p38MAPK)、p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38MAPK)、磷酸化核转录因子-κB p65(phosphorylated-nuclear factor-κB p65,p-NF-κB p65)、核转录因子-κB p65(nuclear factor-κB p65,NF-κB p65)的蛋白表达含量。结果模型组大鼠病理表现为角化过度、角化不全,颗粒层和棘层显著增厚,胶原纤维变粗;模型组肥大细胞数量显著升高,IFN-γ、Foxp3蛋白表达降低、IL-4、IL-17、p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65蛋白表达升高。与模型组比较,三子颗粒组的皮损评分在第6、8、10天均显著减少,病理改变减轻,IFN-γ、Foxp3表达明显增高(P<0.01)、IL-4、p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65表达均显著降低(P<0.05和P<0.01),IL-17表达下降,但差异无统计学意义(P>0.05)。结论三子颗粒可通过抑制肥大细胞过度增生,上调IFN-γ、Foxp3的蛋白水平,降低IL-4、IL-17、p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65的蛋白水平,发挥其对慢性湿疹的治疗作用,初步揭示了三子颗粒外治慢性湿疹的作用机制。Objective To treat the rat model of chronic eczema by Sanzi Granules(三子颗粒)and explore its mechanism of external treatment for chronic eczema.Methods Forty male SD rats were randomly divided into normal group,model group,Sanzi Granules group and Qingpeng Ointment(青鹏软膏)group,with 10 rats in each group.The rat models of chronic eczema were prepared by sensitization with dinitrochlorophenylacetone solution.The model group was given wet compress with normal saline,the Sanzi Granules group was given wet compress with Sanzi Granules lotion,and the Qingpeng Ointment group was externally applied with Qingpeng Ointment.Skin lesion score was used to evaluate the curative effect.HE staining method was used to observe the morphological changes of the skin tissue.The expressions of interferon gamma(IFN-γ)and interleukin-4(IL-4)in skin lesions were detected by immunohistochemical technique.The protein levels of interleukin-17(IL-17),forkhead transcription factor 3(Foxp3),phosphorylated-p38 mitogen activated protein kinase(p-p38MAPK),p38 mitogen activated protein kinase(p38MAPK),phosphorylated-nuclear factor-κB p65(p-NF-κB p65)and nuclear factor-κB p65(NF-κB p65)in skin lesions were detected by Western blot.Results The model group rats showed hyperkeratosis and dyskeratosis,with significant thickening of both the granular and spinous layers,and coarser collagen fibers.In the model group,the number of mast cells was significantly increased,the protein expressions of IFN-γand Foxp3 were decreased,and the protein expressions of IL-4,IL-17,p-p38MAPK/p38MAPK and p-NF-κB p65/NF-κB p65 were increased.Compared with those of the model group,the skin lesion scores of the Sanzi Granules group was significantly reduced on the 6th,8th and 10th day.The alleviated pathological changes and the protein expressions of IFN-γand Foxp3 significantly increased(P<0.01),the protein expressions of IL-4,p-p38MAPK/p38MAPK and p-NF-κB p65/NF-κB p65 were significantly reduced(P<0.05,P<0.01),while the expression of IL-17 decreased,

关 键 词：慢性湿疹 三子颗粒 IFN-γ IL-4 IL-17 FOXP3 p38MAPK/NF-κB p65 

分 类 号：R289.5[医药卫生—方剂学]