通过clodronate改变肠道微生物群和洞察结肠功能:使用短肠综合征大鼠模型的研究
Ayaka Nagano1, Yudai Tsuruno1,2, Koshiro Sugita3
1Department of Pediatric Surgery, Medical and Dental Area, Research and Education Assembly, Research Field in Medical and Health Sciences, Kagoshima University, Kagoshima, Japan.
Pediatric surgery international
|August 18, 2025
概括
克洛德罗纳特在短肠综合征 (SBS) 的老鼠中改变了肠道细菌,可能抑制肝脏疾病. 然而,高剂量可能会对结肠屏障功能产生负面影响.
科学领域:
- 胃肠病学 胃肠病学
- 微生物组研究的研究.
- 药理学 药理学是指药理学的学科.
背景情况:
- 短肠综合征 (SBS) 可以导致肠衰竭相关的肝病 (IFALD).
- 膀核酸载体抑制剂,如克洛德酸,正在研究抑制IFALD.
- 克洛德罗纳酸对SBS肠道微生物群和结肠壁的影响需要进一步阐明.
研究的目的:
- 在SBS的老鼠模型中研究克洛德罗纳酸对肠道微生物群和结肠壁的影响.
- 评估克洛德罗纳酸对微生物群落结构,结肠组织学和基因表达的剂量依赖性影响.
主要方法:
- 在Sprague-Dawley大鼠身上进行了90%的小肠切除,以诱导SBS.
- 鼠被随机分为控制 (SBS/TPN),低剂量克洛德罗纳特 (20 mg/kg/day) 和高剂量克洛德罗纳特 (60 mg/kg/day) 组.
- 分析了便和结肠样本的肠道微生物群组成,紧结基因表达 (Claudin-1) 和炎症标志物 (NLRP3,IL-6).
主要成果:
- 高剂量的克洛德罗纳酸诱导了细菌群体结构的显著异质性,并降低了Firmicutes/Bacteroidota的比率.
- 在高剂量克洛德罗纳特组中,远端结肠密室深度显著增加.
- 在低剂量组的近接结肠中,Claudin-1表达减少,而NLRP3和IL-6表达在各组近接结肠中显著改变.
结论:
- 在SBS老鼠模型中,克洛德罗纳特显著改变了肠道微生物群的组成.
- 这些微生物变化可能有助于抑制IFALD.
- 对结肠屏障的潜在不良影响需要进一步调查.
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