摘要
目的:探究银屑平丸通过调控Notch信号通路对银屑病(PS)小鼠模型皮损及血清炎性因子的调节作用,进一步探讨银屑平丸对PS的治疗机制。方法:将50只BALB/c小鼠按照完全随机原则分为空白对照组、模型组、阿维A胶囊组、银屑平丸组、阿维A胶囊加银屑平丸组(联合用药组)等五组,每组10只。以5%咪喹莫特乳膏涂抹小鼠背部暴露皮肤进行造模,抹药的同时以药物进行干预。实验过程中每日记录各组小鼠的皮损变化,末次给药24 h后,观察每组小鼠皮损变化并予以PS皮损面积及严重程度指数(PASI)评分,酶联免疫吸附测定(ELISA)法检测各组小鼠血清白细胞介素-32(IL-32)、白细胞介素-33(IL-33)、白细胞介素-36(IL-36)等炎性因子的表达水平,Western blot检测皮损组织中Notch受体1(Notch1)、JAGGED1蛋白(Jagged-1)、Hes1转录因子(Hes-1)等蛋白水平的表达。实时定量PCR检测皮损组织中Notch1、Jagged-1、Hes-1等的mRNA的表达。结果:与空白对照组相对比,模型组、阿维A胶囊组、银屑平丸组、联合用药组小鼠背部皮损的严重程度通过计算PASI评分均有显著升高(P<0.05);与模型组相对比,阿维A胶囊组、银屑平丸组、联合用药组小鼠背部皮损的严重程度通过计算PASI评分均有显著降低(P<0.05),其中联合用药组效果最佳(P<0.05);HE染色结果亦证实联合用药组的病理缓解程度最佳(P<0.05);ELISA结果显示,阿维A胶囊组、银屑平丸组、联合用药组均可显著降低小鼠血清IL-32、IL-33、IL-36水平,其中联合用药组效果最佳(P<0.05);Western blot及RT-PCR结果显示,阿维A胶囊组、银屑平丸组、联合用药组均可显著降低小鼠皮损组织的Notch1、Jagged-1、Hes-1蛋白表达及mRNA表达,且联合用药组效果最优(P<0.05)。结论:银屑平丸能有效改善PS小鼠模型的皮损情况,同时与阿维A胶囊联合使用起到协同增效作用,其作用机制可能与银屑平丸能够抑制Notch信号通路相关蛋白表达相关。
Objective:To explore the effect of Yinxieping pills on the skin lesions and serum inflammatory factors in a mouse model of psoriasis(PS)by regulating the Notch signaling pathway,and to further explore the mechanism of Yinxieping pills on PS.Methods:Fifty BALB/cByJ(BALB/c)mice were randomly divided into blank control group,model control group,Avitamin A capsule group,Yinxieping pill group,Avitamin A capsule+Yinxieping pill group(combined medication group)wait for 5 groups,each with 10 animals.Apply 5%imiquimod cream to the exposed skin of the back of the mice to create a model,and intervene with drugs while applying medicine.During the experiment,the skin lesion changes of each group of mice were recorded daily.24 hours after the last administration,the skin lesion changes of each group of mice were observed and the PS lesion area and severity index(PASI)score was given.Enzyme-linked immunosorbent assay(ELISA)method to detect the expression levels of serum interleukin-32(IL-32),interleukin-33(IL-33),interleukin-36(IL-36)and other inflammatory factors in each group of mice,Western blot detect the expression of Notch receptor 1(Notch1),JAGGED1 protein(Jagged-1),Hes1 transcription factor(Hes-1)and other protein levels in skin lesions.Real-time quantitative PCR was used to detect the expression of Notch1,Jagged-1,Hes-1 and other mRNAs in the skin lesions.Results:Compared with the blank control group,the severity of back skin lesions in the model control group,Acitretin capsule group,Yinxieping pill group,and combination medication group was significantly increased by calculating the PASI score(P<0.05);and compared with the model control group,the severity of back skin lesions in the Acitretin capsule group,the Yinxieping pill group,and the combination medication group was significantly reduced by calculating the PASI score(P<0.05),and the combination medication group had the best effect(P<0.05);HE staining results also confirmed that the combined medication group had the best pathological remission(P<0.05);ELISA results showed that the Acitretin capsule group,Yinxieping pill group,and combined medication group could significantly reduce mouse serum levels of IL-32,IL-33,and IL-36,of which the combined medication group has the best effect(P<0.05).Western blot and RT-PCR results show that the Acitretin capsule group,the Yinxieping pill group,and the combined medication group can be used significantly reduced Notch1,Jagged-1,Hes-1 protein expression and mRNA expression in mouse skin lesions,and the combination therapy group had the best effect(P<0.05).Conclusion:Yinxieping pill can effectively improve the skin lesions of PS mouse models.At the same time,it can be used in combination with Acitretin capsule to have a synergistic effect.Its mechanism may be related to Yinxieping pill’s inhibition of Notch signaling pathway related protein expression.
作者
鲍秋羽
席建元
刘梨
BAO Qiuyu;XI Jianyuan;LIU Li(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《陕西中医》
CAS
2021年第8期999-1004,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家自然科学青年科学基金资助项目(81804204)
湖南省教育厅科研项目重点课题(19A363)
湖南省卫生健康委员会科研课题(202104121917)
湖南中医药大学校级科研基金资助项目(JJ201903)。
关键词
银屑病
银屑平丸
NOTCH信号通路
炎性因子
机制研究
Psoriasis
Yinxieping pills
Notch signaling pathway
Inflammatory factors
Mechanism research
