-
特应性皮炎(AD)是一种慢性、复发性、炎症性皮肤病,在全球疾病负担研究(GBD)中以伤残调整寿命年的率衡量时,其造成的疾病负担在非致命性疾病中居于第15位,在所有疾病和损伤中居于59位[1],同时AD造成的负担还与一个国家的国内生产总值呈正相关[2]。在过去的几十年里,亚洲国家居民的AD患病率持续上升,AD亦成为中国当前严重的公共卫生问题之一。中国居民AD的发病率逐年增加,儿童和老年人在亚洲五国均具有较高的AD发病风险,且中国居民的AD发病风险随时期的推进而加重[3]。
消风止痒颗粒现行质量标准收载于《部颁标准》中药成方制剂第十五册,标准编号:WS3-B-2975-98,处方中包括防风、蝉蜕、地骨皮、苍术(炒)、亚麻子、当归、地黄、木通、荆芥、石膏和甘草十一味药材[4]。消风止痒颗粒不仅对接触性荨麻疹作用明显,有缓解皮肤红肿,抑制风团之效[5],还能改善尿毒症患者皮肤瘙痒症状[6]。本研究旨在通过消风止痒颗粒对AD引起的急性瘙痒的缓解作用,探究其可能的作用机制,为中药在止痒方面的研究提供一定的基础和参考依据。
Therapeutic effect of Xiaofeng Zhiyang granules on acute itching in mice with atopic dermatitis by decreasing leukotriene
-
摘要:
目的 建立小鼠特应性皮炎急性瘙痒模型,研究消风止痒颗粒的止痒作用及其机制探讨。 方法 采用诱导法制备特应性皮炎小鼠模型。小鼠每天先后用卡泊三醇和卵清蛋白(OVA)涂抹右耳致敏10 d,然后在小鼠右颊皮内注射OVA进行激发,致使小鼠出现急性瘙痒,记录小鼠激发后30~60 min的抓挠次数。实验分为5组:空白对照组、模型组、消风止痒颗粒低剂量组(7.2 g/kg)和高剂量组(14.4 g/kg)、阳性对照组(孟鲁司特5 mg/kg)。各组于激发前12 h及30 min各灌胃给药一次。通过Elisa检测小鼠血清中白三烯水平,通过流式细胞术检测血液中嗜碱性粒细胞比例及激活状态。 结果 小鼠经致敏和激发后出现明显的抓挠行为,模型组小鼠激发后30~60 min内抓挠次数均值为56次,消风止痒颗粒低和高剂量组小鼠抓挠次数均值分别为42次和23次,较模型组均显著降低(P<0.05)。消风止痒颗粒低、高剂量组血清中白三烯水平和嗜碱性粒细胞比例与模型组比较,均明显降低(P<0.05)。 结论 消风止痒颗粒对小鼠特应性皮炎急性瘙痒具有一定治疗作用,作用机制与其降低特应性皮炎小鼠血清中白三烯水平和降低嗜碱性粒细胞比例有关。 Abstract:Objective To establish a mice model of atopic dermatitis with acute itching and investigate the antipruritic effect and its mechanism of Xiaofeng Zhiyang granules(XFZYG). Methods A mice model of atopic dermatitis was prepared by induction method. Mice were sensitized by calcipotriol and ovalbumin (OVA) applying to the right ear daily for 10 days, and then stimulated by OVA injected intradermally into the right cheek to resulting in acute itching. These mice were divided into 5 groups: blank control group, model group, low dose (7.2 g/kg) and high dose (14.4 g/kg) of XFZYG, and positive control group (montelukast 5 mg/kg). Drugs were administered by gavage at 12 h and 30 min before stimulation. The leukotriene levels in the serum of the mice were measured by Elisa and the basophil ratio and activation status in the blood were measured by flow cytometry. Results The mean number of scratches in the model group was 56 between 30 min and 60 min after stimulation, while the mean number of scratches in the low and high dose of XFZYG groups were 42 and 23 respectively, which were significantly lower than those in the model group (P<0.05). The serum leukotriene levels and the proportion of basophils in the low and high dose of XFZYG groups were significantly lower than those in the model group (P<0.05). Conclusion XFZYG had certain therapeutic effect on acute itching of atopic dermatitis in mice, and the mechanism of its action was related to the reduction of leukotriene level and basophil ratio in serum of mice with atopic dermatitis . -
Key words:
- Xiaofeng Zhiyang granule /
- atopic dermatitis /
- pruritus /
- basophil /
- leukotriene
-
[1] LAUGHTER M R, MAYMONE M B C, MASHAYEKHI S, et al. The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017[J]. Br J Dermatol, 2021, 184(2):304-309. doi: 10.1111/bjd.19580 [2] TSAI T F, RAJAGOPALAN M, CHU C Y, et al. Burden of atopic dermatitis in Asia[J]. J Dermatol, 2019, 46(10):825-834. doi: 10.1111/1346-8138.15048 [3] 樊文龙, 陈东宇, 王红心, 等. 亚洲5国居民1990—2019年特应性皮炎发病趋势年龄-时期-队列分析[J]. 中国公共卫生, 2023, 39(5):650-655. doi: 10.11847/zgggws1138656 [4] 庞威, 樊杰, 孙继泽, 等. 消风止痒颗粒中防风薄层鉴别优化[J]. 人参研究, 2022, 34(6):29-31. [5] 庞博, 徐英莉, 刘晓峰, 等. 氯雷他定与消风止痒颗粒对3种荨麻疹动物模型的药效评价研究[J]. 世界中医药, 2022, 17(21):3026-3032. doi: 10.3969/j.issn.1673-7202.2022.21.008 [6] 葛杰. 消风止痒颗粒、氯雷他定片内服联合血液透析治疗尿毒症皮肤瘙痒症的临床研究[J]. 中华中医药学刊, 2018, 36(6):1497-1499. [7] WANG F, TRIER A M, LI F X, et al. A basophil-neuronal axis promotes itch[J]. Cell, 2021, 184(2):422-440,e17. [8] PUAR N, CHOVATIYA R, PALLER A S. New treatments in atopic dermatitis[J]. Ann Allergy Asthma Immunol, 2021, 126(1):21-31. doi: 10.1016/j.anai.2020.08.016 [9] 邱彩雄, 李康良, 何爽, 等. 皮肤源性急慢性瘙痒动物模型研究进展[J]. 中国医药导报, 2022, 19(33):45-48. [10] SIRACUSA M C, KIM B S, SPERGEL J M, et al. Basophils and allergic inflammation[J]. J Allergy Clin Immunol, 2013, 132(4):789-801;quiz788. doi: 10.1016/j.jaci.2013.07.046 [11] OBATA K, MUKAI K R, TSUJIMURA Y, et al. Basophils are essential initiators of a novel type of chronic allergic inflammation[J]. Blood, 2007, 110(3):913-920. doi: 10.1182/blood-2007-01-068718 [12] NOTI M, WOJNO E D, KIM B S, et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis[J]. Nat Med, 2013, 19(8):1005-1013. doi: 10.1038/nm.3281 [13] POTO R, QUINTI I, MARONE G, et al. IgG autoantibodies against IgE from atopic dermatitis can induce the release of cytokines and proinflammatory mediators from basophils and mast cells[J]. Front Immunol, 2022, 13:880412. doi: 10.3389/fimmu.2022.880412 [14] FOGH K, HERLIN T, KRAGBALLE K. Eicosanoids in skin of patients with atopic dermatitis: Prostaglandin E2 and leukotriene B4 are present in biologically active concentrations[J]. J Allergy Clin Immunol, 1989, 83(2):450-455. doi: 10.1016/0091-6749(89)90132-2 [15] CAPRA V, THOMPSON M D, SALA A, et al. Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: critical update and emerging trends[J]. Med Res Rev, 2007, 27(4):469-527. doi: 10.1002/med.20071 [16] OYOSHI M K, HE R, LI Y T, et al. Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation[J]. Immunity, 2012, 37(4):747-758. doi: 10.1016/j.immuni.2012.06.018 [17] 孟聪聪, 王晓琴, 韩秀萍. 孟鲁司特治疗特应性皮炎研究进展[J]. 中国麻风皮肤病杂志, 2017, 33(12):759-762.