碱性神经酰胺酶1在硫酸钠葡聚糖诱导小鼠溃疡性结肠炎中的保护作用
收稿日期: 2024-10-30
网络出版日期: 2025-01-14
基金资助
国家自然科学青年基金项目(82300032);广东省基础与应用基础研究基金省市联合基金项目(2023A1515110161);广州市科学技术局基础研究计划2024年度基础与应用基础研究专题项目(2024A04J3537);广州市科技局2024年度基础研究计划市校（院）联合资助“登峰医院”项目(2024A03J1145);广州医科大学2023年科研能力提升计划
Protective effect of basic alkaline ceramidase 1 in ulcerative colitis
Received date: 2024-10-30
Online published: 2025-01-14
目的 研究碱性神经酰胺酶1（Acer1）在溃疡性结肠炎（UC）的黏膜屏障和免疫调节中发挥的作用和影响。 方法 通过构建Acer1基因敲除鼠（Acer1 KO），利用硫酸钠葡聚糖 （DSS）连续饮水7 d诱导构建UC模型，对比C57小鼠和Acer1 KO小鼠在UC疾病中症状严重程度，利用RT-PCR和免疫组化检测肠黏膜屏障（ZO-1、Occludin、Claudin、JAMA）的表达水平，通过ELISA评估全身免疫反应水平（IL-1β、IL-6、IL-23、IL-17、IL-10和TNF-α的水平）以及RT-PCR评估肠道炎症浸润程度（TNF-α、IL-1β、IL-6、IL-17、IL-21等）。 结果 自由饮水中C57和Acer1 KO小鼠两组无明显差异；在DSS诱导的UC模型中，与C57小鼠相比Acer1 KO小鼠存活率下降，体质量下降明显，机械屏障和黏液屏障蛋白表达程度显著降低，肠上皮屏障损伤严重，炎症反应强烈，细胞因子浸润明显，结果差异有统计学意义（P < 0.05）。 结论 Acer1通过维持肠黏膜屏障完整性，防御内毒素抑制炎症浸润，在UC发生发展过程中具有延缓疾病进展的作用。
何榕茂 , 方泽扬 , 张芸芸 , 吴友谅 , 梁世秀 , 王斯琪 . 碱性神经酰胺酶1在硫酸钠葡聚糖诱导小鼠溃疡性结肠炎中的保护作用[J]. 实用医学杂志, 2025 , 41(1) : 7 -14 . DOI: 10.3969/j.issn.1006-5725.2025.01.002
Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis （UC）. Methods Acer1 knockout mice （Acer1 KO） were constructed， and the UC model was induced by continuous drinking water of sodium dextran sulfate （DSS） for 7 days， and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared. The expression levels of intestinal mucosal barriers （ZO-1， Occludin， Claudin， JAMA） were detected by RT-PCR and immunohistochemistry. Systemic immune response levels （IL-1b、IL-6、IL-23、IL-17、IL-10， and TNF-a） were assessed by ELISA and intestinal inflammatory infiltration levels （TNF-a、IL-1b、IL-6、IL-17、IL-21， etc.） were assessed by RT-PCR. Results There was no significant difference between C57 and Acer1 KO mice in free drinking water. In the DSS induced UC model， compared with C57 mice， the survival rate of Acer1 KO mice decreased， the weight decreased significantly， the mechanical barrier and mucus barrier protein expression levels decreased significantly， the intestinal epithelial barrier was seriously damaged， the inflammatory response was strong， and the cytokine infiltration was obvious， with statistical differences （P < 0.05）. Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier， preventing endotoxin， and delaying the progression of UC.
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