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南京中医药团队新发现:巴豆酰化修饰通过线粒体自噬缓解溃疡性结肠炎

  • 2026-07-04 06:55:06
南京中医药团队新发现:巴豆酰化修饰通过线粒体自噬缓解溃疡性结肠炎
景杰生物 | 报道
溃疡性结肠炎（UC）是一种慢性、反复发作的炎症性肠病，线粒体稳态失衡在其发病中起关键作用。赖氨酸巴豆酰化（KCr）作为新型酰化修饰，在溃疡性结肠炎中的功能尚不明确。
近日，南京中医药大学附属医院刘史佳、刘鄂湖团队在Exploration（IF=22.5）上在线发表了题为“Modulating Lysine Crotonylation in Ulcerative Colitis Maintains Mitochondrial Homeostasis: Modulating Crotonylation in Ulcerative Colitis”的研究。
该研究通过巴豆酰化修饰组学等技术发现溃疡性结肠炎中TCA循环酶巴豆酰化水平普遍降低；提高整体巴豆酰化修饰水平后，可通过激活PINK1/PARKIN线粒体自噬通路抑制NLRP3炎症小体，从而缓解溃疡性结肠炎。研究还精准锁定柠檬酸合成酶（CS）K375位点为关键修饰靶点。景杰生物为本研究提供了巴豆酰化修饰组学及系列酰化抗体技术支持。
研究对比了溃疡性结肠炎小鼠模型结肠组织的各类酰化修饰后发现，琥珀酰化、丙二酰化、乳酰化修饰均无明显差异，巴豆酰化变化相对显著。结合巴豆酰化修饰组学可以看到，差异修饰蛋白主要定位于线粒体，且高度富集于TCA循环通路，该通路中的CS、DLST等关键酶的巴豆酰化水平在溃疡性结肠炎模型中普遍下调。
图溃疡性结肠炎小鼠模型结肠组织的巴豆酰化修饰组学分析
研究人员利用巴豆酸钠增强整体巴豆酰化修饰后，溃疡性结肠炎小鼠的肠道炎症、体型消瘦等典型症状得到明显改善，体内的炎症因子水平也得以恢复。进一步研究发现，溃疡性结肠炎会造成柠檬酸合成酶催化的柠檬酸显著减少，而上调巴豆酰化修饰水平也可逆转这一现象，提示柠檬酸合成酶是关键效应酶。此外，透射电镜显示，提升巴豆酰化水平还可修复溃疡性结肠炎小鼠的线粒体结构损伤、增加线粒体自噬体数量，同时减轻氧化损伤，抑制肠上皮细胞异常凋亡，全面维持肠道细胞正常生理状态。
图 巴豆酰化修饰水平升高有助于维持线粒体稳态，减少氧化应激并抑制细胞凋亡
机制上，巴豆酰化能够激活经典PINK1/PARKIN线粒体自噬通路，疏通自噬流；进而抑制NLRP3炎症小体活化。当利用氯喹抑制线粒体自噬后，巴豆酰化对NLRP3炎症小体的抑制作用亦随之减弱。印证了线粒体自噬是关键中间环节。前期实验还发现，溃疡性结肠炎模型中柠檬酸合成酶蛋白及其K375位点的巴豆酰化水平同步下降，基因突变实验最终确认，柠檬酸合成酶的K375位点是调控线粒体自噬与肠道炎症的核心位点，为靶向药物研发提供了明确方向。
图 柠檬酸合成酶K375位点巴豆酰化可诱导线粒体自噬并抑制NLRP3炎症小体的激活
综合以上，这项研究首次揭示溃疡性结肠炎中TCA循环酶巴豆酰化水平下调，提升巴豆酰化修饰水平可特异性增强柠檬酸合成酶K375位点巴豆酰化，激活PINK1/PARKIN线粒体自噬，抑制NLRP3炎症小体，维持线粒体稳态，从而缓解溃疡性结肠炎。该研究为溃疡性结肠炎的发病机制提供了新视角，并提出了靶向巴豆酰化修饰的潜在治疗策略。
景杰生物作为新型酰化研究的领跑者，在上万例样品中积累了丰富的新型酰化修饰研究经验和实验方案。可提供“从WB预筛选，新型酰化修饰组学分析，到运用丰富的酰化修饰位点特异性抗体进行功能验证，再到后续的CUT&Tag分析”等全流程服务。景杰生物PTMab抗体产品具有高特异性、高亲和力、高批间一致性等优势，其应用也多次见刊于Cell、 Nature、 Science等国际顶尖杂志。如果您想了解景杰生物研究产品和服务的更多信息，可咨询景杰生物销售工程师、或拨打科服热线400-100-1145。
参考文献：
Liu T, et al. 2026. Modulating Lysine Crotonylation in Ulcerative Colitis Maintains Mitochondrial Homeostasis: Modulating Crotonylation in Ulcerative Colitis. Exploration (Beijing).

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#景杰巴豆酰化 #新型酰化修饰 #溃疡性结肠炎 #线粒体自噬
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  1. CONNECT:[ UseTime:0.001298s ] mysql:host=127.0.0.1;port=3306;dbname=b460;charset=utf8mb4
  2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.001605s ]
  3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.000755s ]
  4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.000660s ]
  5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.001379s ]
  6. SELECT * FROM `set` [ RunTime:0.000528s ]
  7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.001472s ]
  8. SELECT * FROM `article` WHERE `id` = 582191 LIMIT 1 [ RunTime:0.008782s ]
  9. UPDATE `article` SET `lasttime` = 1783240922 WHERE `id` = 582191 [ RunTime:0.033527s ]
  10. SELECT * FROM `fenlei` WHERE `id` = 65 LIMIT 1 [ RunTime:0.000730s ]
  11. SELECT * FROM `article` WHERE `id` < 582191 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.001064s ]
  12. SELECT * FROM `article` WHERE `id` > 582191 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.001382s ]
  13. SELECT * FROM `article` WHERE `id` < 582191 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.020501s ]
  14. SELECT * FROM `article` WHERE `id` < 582191 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.006476s ]
  15. SELECT * FROM `article` WHERE `id` < 582191 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.004958s ]
0.264932s