| 引用本文: | 孙晓静,张义生,徐爱琴,黄毅.肤鲜洗剂通过T细胞介导的免疫平衡对慢性皮炎湿疹小鼠H1R、PAR-2/TRPV1痒信号通路的调控作用[J].中国现代应用药学,2023,40(19):2643-2651. |
| SUN Xiaojing,ZHANG Yisheng,XU Aiqin,HUANG Yi.Regulation of Fuxian Lotion on H1R, PAR-2/TRPV1 Itch Signal Pathway in Mice with Chronic Dermatitis Eczema Through T Cell-mediated Immune Balance[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(19):2643-2651. |
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| 摘要: |
| 目的 探讨辅助性T淋巴细胞1(Th1)/辅助性T淋巴细胞2(Th2)免疫平衡在组胺受体1(histamine receptor 1，H1R)、蛋白酶激活受体2(protease activated receptor 2，PAR-2)/瞬时电位V型1受体(transient receptor potential vanilloid-1，TRPV1)痒信号通路信号传导中的作用及肤鲜洗剂的干预机制。方法 采用BALB/c小鼠60只，适应性喂养3 d后随机分为6组，每组10只，分别为空白对照组，模型对照组，肤鲜洗剂高、中、低剂量组(36，12，4 mg·cm-2)，阳性药物对照组(1 mg·cm-2)，除空白对照组外，其余各组均采用7%和0.5% 2,4-二硝基氯苯丙酮橄榄油溶液多次激发致敏，空白组小鼠腹部及耳部均涂以丙酮溶液对照。激发后24 h开始用药，每天给药2次，连续10 d。测定小鼠耳肿胀度，进行耳变应反应评分，记录搔抓指数，计算小鼠脾脏指数，HE染色观察小鼠耳组织病理学变化，采用ELISA检测血清中肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白细胞介素-1β(interleukin-1 β，IL-1β)、白细胞介素-31(interleukin-31，IL-31)水平，实时荧光定量PCR检测上述免疫因子的mRNA水平，免疫组化法检测H1R、PAR-2、TRPV1的表达。结果 与空白对照组比较，模型对照组小鼠耳厚度、耳变应反应评分、搔抓指数、脾脏指数显著升高(P<0.01)，TNF-α、IL-1β、IL-31蛋白水平和mRNA水平显著升高(P<0.01)，H1R、PAR-2、TRPV1含量明显增加(P<0.01)，并出现明显的慢性皮炎湿疹样病理改变。与模型对照组比较，肤鲜洗剂组可有效减轻小鼠的耳廓肿胀程度、降低耳变应反应评分、搔抓指数、脾脏指数，TNF-α、IL-1β、IL-31蛋白水平和mRNA水平明显降低(P<0.01)；肤鲜洗剂高剂量组、肤鲜洗剂中剂量组、阳性药物对照组H1R含量明显减少(P<0.01)；肤鲜洗剂各剂量组、阳性药物对照组PAR-2、TRPV1含量明显减少(P<0.01)。结论 肤鲜洗剂通过调节Th1/Th2免疫平衡，下调特征性免疫因子TNF-α、IL-1β、IL-31，干预痒信号通路H1R、PAR-2/TRPV1传导，从而实现抗瘙痒和抑制炎症反应，达到治疗慢性皮炎湿疹的目的。 |
| 关键词: 肤鲜洗剂 慢性皮炎 Th1/Th2免疫平衡 H1R、PAR-2/TRPV1痒信号通路 |
| DOI：10.13748/j.cnki.issn1007-7693.20223277 |
| 分类号:R285.5 |
| 基金项目:武汉市卫生和计划生育委员会科研项目(WZ18E02)；武汉市中青年医学骨干人才培养工程(武卫通[2020]55号) |
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| Regulation of Fuxian Lotion on H1R, PAR-2/TRPV1 Itch Signal Pathway in Mice with Chronic Dermatitis Eczema Through T Cell-mediated Immune Balance |
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SUN Xiaojing1, ZHANG Yisheng1, XU Aiqin1, HUANG Yi2
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1.Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430014, China;2.Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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| Abstract: |
| OBJECTIVE To explore the role of Th1/Th2 immune balance in the signal transduction of H1R, PAR-2/TRPV1 itch signal pathway and the intervention mechanism of Fuxian lotion. METHODS There were 60 BALB/c mice randomly divided into 6 groups after 3 days of adaptive feeding, with 10 mice in each group, which were blank control group, model control group, high, medium and low dose group of Fuxian lotion(36, 12, 4 mg·cm-2) and positive drug control group(1 mg·cm-2). Except for the blank control group, all other groups were sensitized with 7% and 0.5% 2,4-dinitrochlorobenzene acetone olive oil solution for multiple times. The abdomen and ears of mice in the blank group were coated with acetone solution for control. The drug was administered 24 hours after challenge, twice a day for 10 consecutive days. The ear thickness and the degree of mice ear swelling were measured and scored. The times of scratching the ears of mice were counted. The spleen index was calculated. HE staining was used to observe the pathological changes in mice ear tissue. The serum TNF-α, IL-1β, IL-31 levels were detected by ELISA, the mRNA level of the above immune factors was detected by realtime PCR, and the expression of H1R, PAR-2 and TRPV1 was detected by immunohistochemistry. RESULTS Compared with the blank control group, the ear thickness, ear allergic reaction score, scratching index, the spleen index of mice in the model control group was significantly increased(P<0.01), the TNF-α, IL-1β, IL-31 protein level and mRNA level were significantly increased(P<0.01), and the contents of H1R, PAR-2 and TRPV1 were significantly increased(P<0.01). There were obvious eczema like pathological changes in chronic dermatitis. Compared with the model control group, Fuxian lotion could effectively reduce the degree of auricle swelling, the score of ear allergic reaction, scratch index and spleen index, significantly reduce the levels of TNF-α, IL-1β, IL-31 protein level and mRNA level(P<0.01). The content of H1R in the high dose group of Fuxian lotion, the medium dose group of Fuxian lotion and the positive drug control group was significantly reduced(P<0.01), and the content of PAR-2 and TRPV1 in all dose groups of Fuxian lotion and the positive drug control group were significantly reduced(P<0.01). CONCLUSION Fuxian lotion can improve chronic dermatitis and eczema by regulating the Th1/Th2 immune balance, down regulating the characteristic immune factor TNF-α, IL-1β, IL-31 and interfering with the itch signal pathway H1R, PAR-2/TRPV1 transmission, so as to anti-itching and inhibit inflammatory response. |
| Key words: Fuxian lotion chronic dermatitis eczema Th1/Th2 immune balance H1R, PAR-2/TRPV1 itch signaling pathway |
