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黄连解毒汤对银屑病小鼠模型中经典Wnt/β-连环蛋白信号通路的干预机制

Intervention Mechanism of Hunag-Lian Jie-Du Decoction on Canonical Wnt/-Catenin Signaling Pathway in Psoriasis Mouse Model.

作者信息

Yang Xuesong, Luo Guangyun, Fu Lan, Huang Hong, Wang Lifen, Yin Lihua, Zhang Xuelian, Wang Tingting, Ma Xuan, Feng Tianyu, Ye Jianzhou

机构信息

Department of Dermatology, The First Affiliated Hospital of Yunnan Traditional Chinese Medicine University, No. 120 Guanghua Rd, Kunming, Yunnan 650021, China.

College of Basic Medicine, Yunnan University of Traditional Chinese Medicine, No. 1076, Yuhua Rd, Kunming, Yunnan 650500, China.

出版信息

Evid Based Complement Alternat Med. 2022 Apr 14;2022:3193572. doi: 10.1155/2022/3193572. eCollection 2022.

DOI:10.1155/2022/3193572
PMID:35463060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9023143/
Abstract

BACKGROUND

Psoriasis is a common chronic inflammatory skin disease with multifactor etiology, characterized by abnormal proliferation and differentiation of keratinocytes. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine prescription with good clinical curative effect on psoriasis. However, its therapeutic mechanisms are still unclear.

METHODS

The psoriasis model of SKH-1 nude mice was established by imiquimod-induced and HLJDD gavage was given. Hematoxylin and eosin staining were used to evaluate pathological morphologies, and immunohistochemistry was used to detect the expressions of Wnt1, -catenin, and c-Myc in psoriasis mice. Western blot was used to examine the expressions of Frizzled-2, LRP5/6, GSK-3, APC, Axin2, TCF4, LEF1, cyclin D1, TBX3, EPHB2, and NOTUM enzyme.

RESULTS

In this study, HLJDD reduced skin erythema and lesions, decreased the thickness of epidermal and downregulated the expressions of Wnt1, -catenin, and c-Myc. Western blot results showed that HLJDD reduced the expressions of Wnt receptors Frizzled-2 and LRP5/6, and Wnt downstream target genes TCF4, LEF1, cyclin D1, TBX3, and EPHB2, while upregulated destruction complex proteins GSK-3, APC, and Axin2.

CONCLUSIONS

HLJDD can effectively treat psoriasis and inhibit the Wnt/-catenin signaling pathway at multiple stages.

摘要

背景

银屑病是一种常见的慢性炎症性皮肤病,病因多因素,以角质形成细胞异常增殖和分化为特征。黄连解毒汤(HLJDD)是一种对银屑病有良好临床疗效的中药方剂。然而,其治疗机制仍不清楚。

方法

通过咪喹莫特诱导建立SKH-1裸鼠银屑病模型,并给予HLJDD灌胃。采用苏木精-伊红染色评估病理形态,免疫组化检测银屑病小鼠中Wnt1、β-连环蛋白和c-Myc的表达。蛋白质免疫印迹法检测卷曲蛋白-2、低密度脂蛋白受体相关蛋白5/6、糖原合成酶激酶-3、腺瘤性息肉病蛋白、轴抑制蛋白2、转录因子4、淋巴细胞增强因子1、细胞周期蛋白D1、T-box转录因子3、表皮生长因子受体酪氨酸激酶2和Notum酶的表达。

结果

在本研究中,HLJDD减轻了皮肤红斑和病变,降低了表皮厚度,并下调了Wnt1、β-连环蛋白和c-Myc的表达。蛋白质免疫印迹结果显示,HLJDD降低了Wnt受体卷曲蛋白-2和低密度脂蛋白受体相关蛋白5/6以及Wnt下游靶基因转录因子4、淋巴细胞增强因子1、细胞周期蛋白D1、T-box转录因子3和表皮生长因子受体酪氨酸激酶2的表达,同时上调了破坏复合物蛋白糖原合成酶激酶-3、腺瘤性息肉病蛋白和轴抑制蛋白2的表达。

结论

HLJDD可有效治疗银屑病,并在多个阶段抑制Wnt/β-连环蛋白信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/b02b6f3a9c1c/ECAM2022-3193572.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/f03da6ef6d9b/ECAM2022-3193572.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/60692cf6f6c5/ECAM2022-3193572.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/e9fd828c4c12/ECAM2022-3193572.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/b02b6f3a9c1c/ECAM2022-3193572.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/f03da6ef6d9b/ECAM2022-3193572.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/60692cf6f6c5/ECAM2022-3193572.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/e9fd828c4c12/ECAM2022-3193572.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce5/9023143/b02b6f3a9c1c/ECAM2022-3193572.004.jpg

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