解毒药与凉血药配伍对咪喹莫特诱导的银屑病样小鼠模型的干预作用

doi:10.3969/j.issn.1006-7795.2018.02.017

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (2): 243-251.doi: 10.3969/j.issn.1006-7795.2018.02.017

解毒药与凉血药配伍对咪喹莫特诱导的银屑病样小鼠模型的干预作用

翟春艳^1,2, 底婷婷², 赵京霞², 王燕², 解欣然², 李雪^2,3, 蒙玉娇^2,3, 李宁飞^2,3, 刘正荣^2,3, 张璐², 张蕾², 王宁², 李萍²

1. 首都医科大学附属北京中医医院, 北京 100010;
2. 北京中医医院北京市中医研究所银屑病中医临床基础研究北京市重点实验室, 北京 100010;
3. 北京中医药大学北京中医医院, 北京 100027

收稿日期:2017-12-19 出版日期:2018-03-21 发布日期:2018-04-14
通讯作者: 李萍 E-mail:xiaor22@ccmu.edu.cn
基金资助:
国家科学自然基金（81330065）。

Effects of Jiedu medicine combined with Liangxue medicine on mice psoriasis-like lesions induced by imiquimod

Zhai Chunyan^1,2, Di Tingting², Zhao Jingxia², Wang Yan², Xie Xinran², Li Xue^2,3, Meng Yujiao^2,3, Li Ningfei^2,3, Liu Zhengrong^2,3, Zhang Lu², Zhang Lei², Wang Ning², Li Ping²

1. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China;
2. Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China;
3. Beijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100027, China

Received:2017-12-19 Online:2018-03-21 Published:2018-04-14
Supported by:
This study was supported by National Natural Science Foundation of China(81330065).

摘要/Abstract

摘要： 目的观察凉血解毒汤与凉血汤对咪喹莫特诱导的银屑病样小鼠模型皮损的影响，并探讨配伍解毒药在银屑病中的作用机制。方法 BALB/c小鼠55只，背部剃毛，采用数字表法随机分为空白对照组、模型组、凉血汤组、凉血解毒汤组和甲氨蝶呤组，采用5%（质量分数）咪喹莫特乳膏背部涂抹诱导皮肤银屑病样模型。观察皮损面积和疾病严重程度（psoriasis area and severity index，PASI）并评分，光镜下观察皮损组织形态学变化及表皮层厚度；采用皮肤水分油分测试笔检测小鼠背部皮肤水分和油分含量；采用免疫组织化学染色法观察小鼠皮损中增生细胞核抗原（proliferating cell nuclear antigen，PCNA）和T淋巴细胞表面标志CD3表达；采用RT-PCR技术检测皮损中白细胞介素-17（interleukin-17，IL-17）、IL-23及IL-1β mRNA表达。结果与模型组相比，凉血解毒汤和凉血汤组小鼠皮损PASI评分及表皮厚度均明显降低、PCNA阳性细胞百分比下降、CD3阳性T细胞表达个数减少、IL-1β mRNA相对表达量相对下降（P<0.05）；此外凉血解毒汤还可使小鼠皮损中水分（16.980±2.739）、油分（7.750±1.209）含量有效升高（P<0.05），IL-17、IL-23 mRNA相对表达量明显下降（P<0.05），对皮损PASI评分及表皮厚度、PCNA阳性细胞百分比（5.66±0.057）和CD3阳性T细胞表达个数（10.670±0.193）的影响也更为显著（P<0.01）。结论凉血解毒汤与凉血汤均可抑制IL-1β mRNA的表达，减少炎性浸润，改善咪喹莫特诱导的银屑病样炎性反应皮损；而配伍解毒药的凉血解毒汤，则可进一步通过抑制IL-23、IL-17的表达，提升其在改善皮肤屏障功能及皮损组织形态变化、减缓表皮角质形成细胞增生、减少角化不全细胞及降低炎性反应浸润程度等方面的干预作用，从而缓解咪喹莫特诱导的银屑病样皮损改变，提示解毒中药对炎性反应及相关因子的抑制作用可能是其治疗银屑病的潜在机制之一。

关键词: 银屑病, 凉血汤, 凉血解毒汤, 白细胞介素-17, 白细胞介素-23

Abstract: Objective To observe the effects of Liangxue Jiedu (LXJD) decoction and Liangxue(LX)decoction on mice psoriasis-like lesions induced by imiquimod (IMQ), and further explore the the mechanism of compatibility of Jie Du medicine in psoriasis.Methods BALB/c mice (n=55) were randomly divided into 5 groups:control group, model group, LX groups, LXJD groups, and methotrexate (MTX) group. The model was induced by 5% IMQ daily. On day 7, to observe the psoriasis area and severity index(PASI) and score, observed lesions morphological changes and epidermal layer thickness under light microscope; The skin barrier function was evaluated by testing oil and water component in the skin. The histology and epidermal thicknesses were observed under high microscope. The expressions of proliferating cell nuclear antigen (PCNA) and CD3 were detected by immunohistochemical staining. And detecting interleukin-17 (IL-17) mRNA,IL-23 mRNA andIL-1β mRNA were detected by RT-PCR. Results The cutaneous symptoms were alleviated in LX and LXJD groups compared with those in model group accompanied with PASI scores decreased; the means of epidermis thickness in LX and LXJD groups were less than that in model group; compared with model group,the percentages of PCNA positive cells and the numbers of CD3 positive cells in LX and LXJD groups were reduced(P<0.05); meanwhile, the relative expressions of IL-1β mRNA in LX and LXJD groups were decreased compared with that in model group(P<0.05). In the above indexes, LXJD group was better than LX group(P<0.01). In addition the LXJD decoction can make the moisture content (16.980±2.739) and oil content (7.750±1.209) in the lesions of mice increased (P<0.05). The relative expression of IL-17 and IL-23 mRNA also decreased (P<0.05). In some indexes like PASI scores, epidermis thickness, the percentages of PCNA positive cells (5.66±0.057) and the numbers of CD3 positive cells (10.670±0.193), LXJD group was better than LX group (P<0.01). Conclusion LXJD decoction and LX decoction can inhibit the expression of IL-1 β, reduce inflammatory infiltration and thereby improving imiquimod-induced mice psoriasis-like lesions. Jiedu medicine may play a crucial role through the inflammatory axis of IL-17 and IL-23 on LXJD group which can better alleviate psoriasis like lesions and further improve the skin barrier function. It is suggested that the inhibitory effect of the Jie Du medicine on the related inflammatory factors may be a potential mechanism for the treatment of psoriasis.

Key words: psoriasis, Liangxue decoction, Liangxue Jiedu decoction, interleukin-17, interleukin-23

中图分类号:

R289.5

翟春艳, 底婷婷, 赵京霞, 王燕, 解欣然, 李雪, 蒙玉娇, 李宁飞, 刘正荣, 张璐, 张蕾, 王宁, 李萍. 解毒药与凉血药配伍对咪喹莫特诱导的银屑病样小鼠模型的干预作用[J]. 首都医科大学学报, 2018, 39(2): 243-251.

Zhai Chunyan, Di Tingting, Zhao Jingxia, Wang Yan, Xie Xinran, Li Xue, Meng Yujiao, Li Ningfei, Liu Zhengrong, Zhang Lu, Zhang Lei, Wang Ning, Li Ping. Effects of Jiedu medicine combined with Liangxue medicine on mice psoriasis-like lesions induced by imiquimod[J]. Journal of Capital Medical University, 2018, 39(2): 243-251.

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解毒药与凉血药配伍对咪喹莫特诱导的银屑病样小鼠模型的干预作用

Effects of Jiedu medicine combined with Liangxue medicine on mice psoriasis-like lesions induced by imiquimod

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