基于细胞焦亡途径探讨高良姜素对小鼠溃疡性结肠炎的保护机制

doi:10.3760/cma.j.issn.1007-1245.2023.11.015

国际医药卫生导报 ›› 2023, Vol. 29 ›› Issue (11): 1546-1552.DOI: 10.3760/cma.j.issn.1007-1245.2023.11.015

基于细胞焦亡途径探讨高良姜素对小鼠溃疡性结肠炎的保护机制

王浩坤^1,2 刘成霞^1,2

¹滨州医学院附属医院消化病研究所，滨州　256600；²滨州医学院附属医院消化内科，滨州　256600

收稿日期:2022-11-24 出版日期:2023-06-01 发布日期:2023-06-25
通讯作者: 刘成霞，Email：phdlcx@163.com
基金资助:
北京医卫健康公益基金会医学科学研究基金（B187004）

Investigating the protective mechanism of galangin against ulcerative colitis in mice based on the pathway of pyroptosis

Wang Haokun^1,2, Liu Chengxia^1,2

¹Institute of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, China; ²Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, China

Received:2022-11-24 Online:2023-06-01 Published:2023-06-25
Contact: Liu Chengxia, Email: phdlcx@163.com
Supported by:
Medical Science Research Fund of Beijing Medical and Health Foundation (B187004)

摘要/Abstract

摘要：

目的　探讨高良姜素（galangin）对葡聚糖硫酸钠（DSS）诱导小鼠溃疡性结肠炎的保护作用及可能机制，为溃疡性结肠炎的治疗提供新的方法。方法　将C57BL/6小鼠30只分为5组，每组6只，分别为正常对照组、模型组、高良姜素组（40 mg·kg^-1·d^-1）、美沙拉嗪组（0.5 g·kg^-1·d^-1）、高良姜素联合美沙拉嗪组（高良姜素40 mg·kg^-1·d^-1、美沙拉嗪0.5 g·kg^-1·d^-1）。3.5% DSS溶液连续干预7 d建立小鼠急性溃疡性结肠炎模型，造模的同时药物干预，并计算疾病活动指数（disease activity index，DAI），第8天麻醉后处死所有小鼠，进行组织损伤指数（histological index，HI）评分。酶联免疫吸附实验（enzyme linked immunosorbent assay，ELISA）检测血清中白细胞介素（IL）-1β和IL-18的含量，免疫组化法检测结肠组织中NLRP3、半胱氨酸天冬氨酸蛋白酶（Caspase）-1的表达。采用One-way ANOVA。结果　模型组DAI及HI评分均明显升高，其他治疗组均有不同程度下降（均P<0.05）。免疫组化结果表明高良姜素降低了NLRP3和Caspase-1的表达（均P<0.01），且联合美沙拉嗪效果更加显著（均P<0.05）。ELISA结果表明高良姜素可以抑制IL-1β、IL-18的表达（均P<0.05），且联合美沙拉嗪作用更加明显（均P<0.05）。结论　高良姜素可以减轻DSS诱导的小鼠溃疡性结肠炎，且联合美沙拉嗪效果更加显著，其保护作用部分是通过抑制细胞焦亡实现的。

关键词:

溃疡性结肠炎, 炎症性肠病, 高良姜素, 细胞焦亡, NLRP3炎性小体, 动物实验

Abstract:

Objective　To explore the protective effect and possible mechanism of galangin on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice, and provide a new method for the treatment of ulcerative colitis. Methods　Thirty C57BL/6 mice were divided into 5 groups with 6 mice in each group, namely the normal control group, the model group, the galangin group (40 mg·kg^-1·d^-1), the mesalazine group (0.5 g·kg^-1·d^-1), and the galangin combined with mesalazine group (galangin 40 mg·kg^-1·d^-1 and mesalazine 0.5g·kg^-1·d^-1). A mouse model of acute ulcerative colitis was established by continuous intervention with 3.5% DSS solution for 7 days, and drug intervention was performed at the same time as the model was established. The disease activity index (DAI) was calculated. All the mice were sacrificed after anesthesia on the 8th day, and the histological index (HI) score was performed. The levels of interleukin (IL)-1β and IL-18 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3 and cysteinyl aspartate specific proteinase (Caspase)-1 in the colon tissue were detected by immunohistochemistry. One-way ANOVA was used. Results　The DAI and HI scores in the model group were significantly increased, while those in the other treatment groups were decreased to varying degrees (all P<0.05). Immunohistochemical results showed that galangin reduced the expressions of NLRP3 and Caspase-1 (both P<0.01), and the combined effect of mesalazine was more significant (both P<0.05). ELISA results showed that galangin could inhibit the expressions of IL-1β and IL-18 (both P<0.05), and the combined effect of mesalazine was more significant (both P<0.05). Conclusion　Galangin can alleviate DSS-induced ulcerative colitis in mice, especially in combination with mesalazine, and its protective effect is partly achieved by inhibiting the pyroptosis.

Key words:

Ulcerative colitis, Inflammatory bowel disease, Galangin, Pyroptosis, NLRP3 inflammasome, Animal , experiment

王浩坤刘成霞.

基于细胞焦亡途径探讨高良姜素对小鼠溃疡性结肠炎的保护机制 [J]. 国际医药卫生导报, 2023, 29(11): 1546-1552.

Wang Haokun, Liu Chengxia.

Investigating the protective mechanism of galangin against ulcerative colitis in mice based on the pathway of pyroptosis [J]. International Medicine and Health Guidance News, 2023, 29(11): 1546-1552.

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基于细胞焦亡途径探讨高良姜素对小鼠溃疡性结肠炎的保护机制

Investigating the protective mechanism of galangin against ulcerative colitis in mice based on the pathway of pyroptosis

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