龙胆泻肝汤通过H1R/TRPV1、PAR-2/TRPV1和P38MAPK通路干预湿疹大鼠的作用机制研究  

Protective Effect of Longdan Xiegan Decoction on Eczema Rats Regulating H1R/TRPV1, PAR-2/TRPV1 and P38MAPK Signal Pathway

作　　者：张明昊[1] 薛鹏坤 赵盈盈 高一盈 董文霞 马伟洋 王珍[1] 张超[3] Zhang Minghao;Xue Pengkun;Zhao Yingying;Gao Yiying;Dong Wenxia;Ma Weiyang;Wang Zhen;Zhang Chao(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Graduate School,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学医学院,郑州450046 [2]河南中医药大学药学院,郑州450046 [3]河南中医药大学研究生院,郑州450046

出　　处：《世界科学技术-中医药现代化》2022年第6期2331-2339,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河南中医药大学大学生创新学习项目(YXCX[2019]-1):基于H1R、PAR-2/TRPV1与P38MAPK/NF-κB信号通路的龙胆泻肝汤治疗慢性湿疹的作用机制研究,负责人:赵盈盈。

摘　　要：目的 基于H1R/TRPV1、PAR-2/TRPV1和P38MAPK通路探讨龙胆泻肝汤对湿疹大鼠的保护作用及相关机制。方法 60只大鼠按体质量随机分为正常组、模型组、氯雷他定组(1 mg·kg^(-1))和龙胆泻肝汤低、中、高剂量组(6.3g·kg^(-1)、12.6g·kg^(-1)、25.2g·kg^(-1)),每组10只。除正常组外,其余各组大鼠采用二硝基氯苯(DNCB)建立湿疹模型,然后各组大鼠灌胃相应药物干预,1次/天,连续干预21天。末次给药后,测定大鼠耳肿胀度;采用苏木素-伊红(HE)染色法观察各组大鼠背部皮肤病理学变化;采用免疫组织化学法检测大鼠皮肤组织H1R、PAR-2、TRPV1蛋白水平;采用蛋白质印迹(WB)法检测大鼠皮肤组织P38MAPK、PP38MAPK蛋白水平。结果 与正常组比较,模型组大鼠耳肿胀度显著增加(P<0.05)且背部皮肤出现湿疹病理变化;皮肤组织中H1R、PAR-2、TRPV1水平与p-P38MAPK/P38MAPK比值显著升高(P<0.05);与模型组比较,氯雷他定组和龙胆泻肝汤低、中、高剂量组耳肿胀度显著减小(P<0.05)且病变程度减轻;皮肤组织中H1R、PAR-2、TRPV1水平与p-P38MAPK/P38MAPK比值显著降低(P<0.05)。结论 龙胆泻肝汤对湿疹大鼠具有保护作用,其机制可能与抑制H1R/TRPV1、PAR-2/TRPV1和P38MAPK通路有关。Objective To study the protective effect and mechanism of Longdan Xiegan Decoction on eczema model in rats. Methods Totally 60 healthy rats were randomly divided into normal, model, loratadine 1mg·kg^(-1), and Longdan Xiegan Decoction 6.3g·kg^(-1), 12.6g·kg^(-1), 25.2g·kg^(-1)groups, with 10 rats in each group. Eczema rat model was induced by DNCB. The rats in each group were given the corresponding dose of drugs daily by gavage, and the intervention was continued for 21 days. After the last administration, the ear swelling was measured;hematoxylin-eosin(HE) staining method was used to observe the histopathological characteristics dorsal skin;immunohistochemistry was used to determine the levels of H1R, PAR-2, TRPV1;western blotting(WB) was used to determine the levels of P38MAPK and P-P38MAPK.Results Compared with normal group, there was pathological changes in dorsal skin and the ear swelling was significantly increased(P<0.05);and the level of H1R, PAR-2, TRPV1 protein and the ratio of p-P38MAPK/P38MAPK were significantly higher(P<0.05) in the model group. Compared with the model group, loratadine and Longdan Xiegan Decoction(6.3 g·kg^(-1), 12.6 g·kg^(-1), 25.2 g·kg^(-1)) decreased the ear swelling and the level of H1R, PAR-2, TRPV1 protein and the ratio of p-P38MAPK/P38MAPK(P<0.05), improved the histopathological changes of the eczema rats. Conclusion Longdan Xiegan Decoction has the protective effect on eczema rats, and its mechanism is related to inhibition H1R/TRPV1, PAR-2/TRPV1 and P38MAPK signal pathway.

关 键 词：龙胆泻肝汤 湿疹 H1R/TRPV1 PAR-2/TRPV1 P38MAPK 大鼠 

分 类 号：R285.5[医药卫生—中药学]