| 姜梦雪,王雨昕,葛美丽,等.AnxA1缺失加重DSS诱导小鼠溃疡性结肠炎及其与NF-?B/p65信号的相关性研究[J].安徽医药,待发表. |
| AnxA1缺失加重DSS诱导小鼠溃疡性结肠炎及其与NF-?B/p65信号的相关性研究 |
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| 投稿时间：2026-08-15 录用日期：2026-10-13 |
| DOI： |
| 中文关键词: 膜联蛋白A1（AnxA1） DSS 溃疡性结肠炎 NF-?B/p65 肠黏膜屏障 |
| 英文关键词: |
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| 中文摘要: |
| 探讨AnxA1缺失对DSS诱导小鼠溃疡性结肠炎的作用，并通过RAW264.7细胞初步分析其与NF-?B/p65信号的相关性 。方法 动物实验采用野生型（WT）及AnxA1敲除纯合小鼠（AnxA1-KO），给予3% DSS自由饮用7天建立UC模型。观察小鼠结肠长度、体重变化、疾病活动指数（DAI）；HE染色观察结肠组织病理损伤情况；免疫组化检测结肠组织紧密连接蛋白以及p-p65蛋白的表达；RT-qPCR检测炎症因子表达；Western blotting检测结肠组织中p65、p-p65蛋白表达水平。以脂多糖（LPS）诱导RAW264.7细胞炎症模型，通过AnxA1敲低或过表达，结合RT-qPCR、Western blotting、免疫荧光及Co-IP检测炎症因子表达、p-p65及蛋白复合情况。结果 与WT-DSS组相比，AnxA1-KO-DSS组小鼠结肠长度缩短，体重下降更明显，DAI评分升高；结肠组织损伤严重；ZO-1、Occludin、Claudin-1表达降低；促炎因子mRNA的表达升高；p-p65蛋白免疫组化阳性信号明显增强，结肠组织p-p65蛋白表达升高。细胞实验结果显示，AnxA1敲低增强LPS诱导的炎症因子表达及p65磷酸化，而AnxA1过表达则作用相反。Co-IP结果提示AnxA1可与p65共存在于同一蛋白复合物。结论 AnxA1缺失可加重DSS诱导小鼠溃疡性结肠炎及肠黏膜屏障损伤，并观察到NF-?B/p65磷酸化活化增强；体外实验提示 AnxA1可能参与NF-?B/p65相关炎症调控，二者的因果机制尚待进一步验证。 |
| 英文摘要: |
| Abstract: Objective To investigate the effect of AnxA1 in DSS-induced ulcerative colitis in mice, and preliminarily analyze its correlation with NF-?B/p65 signal
through RAW264.7 cells. Methods Animal experiments were conducted using wild-type (WT) and AnxA1 knockout homozygous mice (AnxA1-KO), and a UC model was established by administration of 3% DSS in drinking water for 7 days. Changes of colon length, body weight, and disease activity index (DAI) in mice were observed; HE staining was used to observe pathological damage in colon tissue; Immunohistochemistry was performed to detect the expression of tight junction proteins and p-p65 in colon tissue; RT-qPCR was used to detect the expression of inflammatory factors; Western blotting was used to detect the expression levels of p65 and p-p65 in colon tissue. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide (LPS), and AnxA1 was knocked down or overexpressed. The expression of inflammatory factors, p-p65, and protein complex formation were detected by RT-qPCR, Western blotting, immunofluorescence, and Co-IP. Results Compared with the WT-DSS group, the AnxA1-KO-DSS group showed shorter colon length, more significant weight loss, and increased DAI scores,as well as severe colonic tissue damage and reduced expression of ZO-1, Occludin, and Claudin-1; the expression of pro-inflammatory cytokine mRNA was elevated;The immunohistochemistry positive signal of p-p65 protein was significantly increased, and the protein expression level of p-p65 in colon tissue was elevated.. The cell experiment results showed that knocking down AnxA1 enhanced LPS-induced inflammatory cytokine expression and p65 phosphorylation, while overexpression of AnxA1 had the opposite effect. The Co-IP results suggested that AnxA1 could coexist with p65 in the same protein complex. Conclusion The absence of AnxA1 could exacerbate ulcerative colitis and intestinal mucosal barrier damage induced by DSS in mice, and an enhanced phosphorylation and activation of NF-?B/p65 was observed. In vitro experiments suggest that AnxA1 may be involved in the regulation of NF ?B/p65 related inflammation; the causal mechanism between the two remains to be further verified. |
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