用X-aptamer准细胞外CIRP显示在急性胰腺炎中具有治疗潜力
Wuming Liu1,2, Jianbin Bi1,3, Yifan Ren1,4
1National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
iScience
|June 26, 2023
概括
严重的急性胰腺炎 (AP) 涉及增加的冷诱导性RNA结合蛋白 (CIRP). 用X-aptamer准细胞外CIRP显示了减少胰腺损伤和炎症的治疗潜力.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 严重的急性胰腺炎 (AP) 的死亡率很高.
- 细胞外冷诱导性RNA结合蛋白 (CIRP) 在炎症条件下充当与损伤相关的分子模式.
研究的目的:
- 调查CIRP在AP病变发生中的作用.
- 为了评估针对细胞外CIRP的X-aptamers治疗AP治疗的疗效.
主要方法:
- 在AP小鼠模型中测量血清CIRP度.
- 利用重组CIRP诱导胰腺细胞损伤.
- 采用一个基于珠的X-aptamer库来识别CIRP结合的aptamer (XA-CIRP).
- 在实验室和体内评估了XA-CIRP阻断CIRP-TLR4相互作用和减轻CIRP诱导损伤的能力.
主要成果:
- 在AP小鼠中,血清CIRP水平显著升高.
- 重组CIRP诱导了胰腺细胞中的线粒体损伤和ER压力.
- 在CIRP淘汰赛小鼠中,胰腺损伤和炎症的减少.
- XA-CIRP特别结合CIRP,阻止其与TLR4的相互作用,并在体外和体内减少CIRP诱导的胰腺损伤.
结论:
- 细胞外CIRP在急性胰腺炎的发病过程中起着重要作用.
- 用X-aptamers (如XA-CIRP) 准细胞外CIRP是一种有前途的治疗策略,用于管理AP.
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