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四神丸通过抑制 wnt/β-连环蛋白通路减轻实验性慢性结肠炎的药理机制。

Pharmacological mechanism of Sishen Wan attenuated experimental chronic colitis by inhibiting wnt/β-catenin pathway.

机构信息

School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.

Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.

出版信息

J Ethnopharmacol. 2019 Aug 10;240:111936. doi: 10.1016/j.jep.2019.111936. Epub 2019 May 10.

DOI:10.1016/j.jep.2019.111936
PMID:31078692
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Sishen Wan (SSW) is a commercial and frequently used Chinese patent medicine listed in the Chinese Pharmacopeia, which is usually used to treat chronic colitis.

AIM OF THE STUDY

We explored the pharmacological mechanism of Sishen Wan attenuated experimental chronic colitis by inhibiting Wnt/β-catenin pathway.

MATERIALS AND METHODS

Experimental chronic colitis was induced by trinitrobenzene sulfonic acid (TNBS). The therapeutic effect of SSW were analyzed by index of colonic weight, colonic length, pathological score. Cytokines expression were analyzed by ELISA, while the apoptosis level was checked by TUNEL staining. These proteins of Wnt/β-catenin signaling pathway was analyzed by Western blot assay.

RESULTS

Rats with TNBS-induced chronic colitis were treated by SSW for 10 days. The efficacy of SSW was demonstrated by improved macroscopic and microscopic colonic damage. SSW increased the level of ATP in colonic mucosa, while SSW inhibited β-catenin, ubiquitination of Nemo-like-kinase-associated ring finger protein and T-cell factor, and expression of Wnt/β-catenin downstream proteins (including c-Myc, cyclo-oxygenase-2, cyclin D1, survivin, signal transducer and activator of transcription 3 and zipper-interacting protein kinase), and improved lymphoid enhancer factor ubiquitination and β-TrCP activity, followed by excessive apoptosis of colonic epithelial cells.

CONCLUSIONS

SSW effectively attenuated experimental chronic colitis induced by TNBS, which was realized by inhibition of the Wnt/β-catenin signaling pathway.

摘要

民族药理学相关性

四神丸(SSW)是一种商业上常用的中成药,列于《中国药典》中,通常用于治疗慢性结肠炎。

研究目的

我们通过抑制 Wnt/β-catenin 通路,研究四神丸减轻实验性慢性结肠炎的药理机制。

材料与方法

采用三硝基苯磺酸(TNBS)诱导实验性慢性结肠炎。通过结肠重量指数、结肠长度和病理评分分析 SSW 的治疗效果。通过 ELISA 分析细胞因子表达,通过 TUNEL 染色检查细胞凋亡水平。通过 Western blot 分析 Wnt/β-catenin 信号通路的这些蛋白。

结果

用 SSW 治疗 TNBS 诱导的慢性结肠炎大鼠 10 天。SSW 通过改善宏观和微观结肠损伤来证明其疗效。SSW 增加了结肠黏膜中的 ATP 水平,同时抑制了β-catenin、Nemo-like-kinase-associated 环指蛋白的泛素化和 T 细胞因子,以及 Wnt/β-catenin 下游蛋白(包括 c-Myc、环氧化酶-2、细胞周期蛋白 D1、存活素、信号转导和转录激活因子 3 和拉链相互作用蛋白激酶)的表达,并改善了淋巴增强因子的泛素化和β-TrCP 活性,随后导致结肠上皮细胞过度凋亡。

结论

SSW 通过抑制 Wnt/β-catenin 信号通路,有效减轻 TNBS 诱导的实验性慢性结肠炎。

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