本研究發現，在實驗性結腸炎中，硫化氫可通過增加核糖體蛋白S20的硫氫化水平，促進其與MCM2 mRNA結合，維持腸上皮增殖，從而保護腸屏障修復功能。

在現代快節奏的生活中，腸炎尤其是潰瘍性結腸炎（UC）已成為困擾眾多人群的消化科常見病?；颊叩哪c屏障功能顯著受損，不僅影響營養吸收，還可能引發一系列并發癥，嚴重降低生活質量。

近日，Sci Rep發表的一項研究Hydrogen sulfide preserves intestinal barrier repair function through sulfhydration of RPS20 in experimental colitis揭示了硫化氫（H?S）在維持腸屏障修復功能中的關鍵作用，為結腸炎的臨床治療提供了全新的思路。

潰瘍性結腸炎患者的腸屏障如同被破壞的城墻，失去了阻擋有害物質的能力。而H?S作為一種氣體信號分子，此前已被證實能在多種疾病中發揮保護作用，包括減輕結腸炎中的炎癥反應。在這項研究中，科研團隊通過建立DSS誘導的結腸炎小鼠模型、培養小鼠結腸上皮類器官，并結合H&E染色和質譜分析等技術，深入探究了H?S對腸屏障的保護機制。

研究結果顯示，外源性H?S供體GYY4137能顯著緩解UC小鼠模型的癥狀，并維持微小染色體維持復合體組分2（MCM2）的表達。當敲低胱硫醚β-合酶（CBS）時，小鼠結腸中硫氫化核糖體蛋白S20（RPS20-ssh）和MCM2的表達均降低。細胞實驗進一步表明，起作用的是RPS20的硫氫化表達，而非其總表達量。

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圖 1. CBS敲除加劇DSS誘導的實驗性結腸炎

深入機制研究發現，CBS-H?S軸會增加RPS20的硫氫化水平，進而增強RPS20與MCM2 mRNA的結合，促進腸上皮細胞增殖。在動物實驗中，與野生型（WT）小鼠相比，CBS+/-雜合小鼠在DSS誘導下結腸炎更嚴重，腸通透性增加，腸上皮修復功能顯著降低，且RPS20的硫氫化水平和MCM2表達均下降。而給予GYY4137后，這些情況得到明顯改善。

圖 2. CBS-H?S軸減輕UC中的腸屏障破壞并維持腸上皮增殖

在類器官培養實驗中，WT小鼠的結腸類器官在生長過程中，總類器官數量、單芽類器官和多芽類器官數量均顯著多于CBS+/-小鼠組，且CBS+/-組的囊狀類器官比例更高，通透性也更強，充分證明了CBS-H?S軸對結腸上皮類器官生長和通透性完整性的維持作用。

圖 3. CBS-H?S軸維持小鼠腸上皮類器官的增殖

從分子層面來看，科研團隊通過轉錄組測序和生物信息學分析，發現CBS敲除會導致MCM2表達降低，而MCM2作為細胞增殖的關鍵調控因子，其表達變化直接影響腸上皮細胞的修復能力。進一步研究證實，H?S通過硫氫化RPS20的Cys70位點，增加RPS20與MCM2 mRNA的結合，穩定MCM2 mRNA，從而促進MCM2表達，最終維持腸上皮細胞的增殖。

圖 4. CBS-H?S軸維持結腸上皮中MCM2的表達

這項研究首次明確了CBS-H?S軸通過調控RPS20-MCM2軸來維持腸屏障修復功能的分子機制，為結腸炎的治療提供了極具潛力的新靶點。H?S作為內源性氣體信號分子，其供體藥物如GYY4137有望成為改善腸屏障功能、促進腸上皮修復的新型治療藥物。未來，隨著對這一機制的深入研究和相關藥物的開發，或許能為眾多潰瘍性結腸炎患者帶來福音，讓他們重新擁有健康的腸屏障，享受無“炎”的生活。