中文摘要：

NOD樣受體蛋白3（NLRP3）炎癥小體在人類急性和慢性肝病中發揮著至關重要的作用。然而，NLRP3在肝臟再生中的作用及其細胞特異性貢獻仍不清楚。在這里，我們發現，在70%部分肝切除（PHx）小鼠模型和臨床數據中，NLRP3在肝臟再生早期階段高度激活。全球性NLRP3缺失或藥理學阻斷NLRP3顯著增強了肝臟再生，而NLRP3過表達在PHx后則損害了肝臟再生。此外，與肝細胞特異性敲除（Nlrp3Δhep）不同，髓系特異性敲除Nlrp3的小鼠（Nlrp3Δmye）顯示肝臟再生明顯改善，與對照組（Nlrp3fl/fl）相比有顯著差異。在機制上，Nlrp3缺失促進了髓系-上皮-受體酪氨酸激酶（MerTK）介導的凋亡細胞清除作用，從而誘導巨噬細胞向促修復的Ly6C低表型轉化。值得注意的是，通過MCC950抑制NLRP3能夠有效逆轉高脂飲食小鼠PHx后肝臟再生受損的情況。我們的研究結果為術后肝衰竭的預防和治療提供了潛在的治療策略。

英文摘要：

The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in human acute and chronic liver diseases. However, the role and cell-specific contribution of NLRP3 in liver regeneration remains unclear. Here, we found that NLRP3 was highly activated during the early stage of liver regeneration via 70% partial hepatectomy (PHx) mice model and clinical data. Global NLRP3 depletion or pharmacologically blocking NLRP3 significantly enhanced liver regeneration, while NLRP3 overexpression impaired it after PHx. Furthermore, mice with myeloid-specific knockout of Nlrp3 (Nlrp3Δmye), rather than hepatocyte-specific knockout (Nlrp3Δhep), showed improved liver regeneration compared to control (Nlrp3fl/fl). Mechanistically, deficiency of Nlrp3 promoted myeloid-epithelial-reproductive tyrosine kinase (MerTK)–mediated efferocytosis, thereby inducing macrophages toward a pro-reparative Ly6Clo phenotype. Notably, NLRP3 inhibition by MCC950 effectively reversed the impairment of liver regeneration after PHx in mice fed a high-fat diet. Our findings provide a potential therapeutic strategy for the prevention and treatment of post-hepatectomy liver failure.

論文信息：

論文題目：NLRP3 inflammasome constrains liver regeneration through impairing MerTK-mediated macrophage efferocytosis

期刊名稱：Science Advances

時間期卷：Vol 1, Issue 1(2025)

在線時間：2025年1月1日

DOI：doi.org/10.1126/sciadv.adq5786

產品信息：

貨號：CP-005-005

規格：5ml+5ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質體在小鼠創肝臟再生模型種清除肝臟巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：NLRP3 炎癥小體通過抑制 MerTK 介導的巨噬細胞胞葬作用，進而限制肝臟再生。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：

To generate the PHx model, mice were subjected to 70% PHx as our previous description . For macrophage depletion, 200 μl of CLs (Liposoma) and control liposomes were intraperitoneally injected 4 hours before PHx. For hepatic NLRP3 overexpression, the mice were injected with AAV8-NLRP3 (AAV-OE) or AAV-8-NTC (AAV-BL) (General Biology) at a dosage of 1 × 1012 vector genomes (vg) per mouse intravenously 20 days before PHx operation. For NLRP3 inhibition, MCC950 (TargetMol, no. T3701) was administrated intraperitoneally to a concentration of 20 μg/kg 2 hours before PHx. For MerTK inhibition, UNC2025 (TargetMol, no. T7007) was administrated intraperitoneally to a concentration of 50 mg/kg 2 hours before and 24 hours after PHx. For IL-1β inhibition, IL-1β neutralizing antibody (R&D Systems, no. AF-401-NA) was administrated intraperitoneally to a concentration of 10 mg/kg 4 hours before PHx. For macrophage depletion, CLs (200 μl; Yeasen, no. 40337ES08) and control liposomes (200 μl; Yeasen, no. 40338ES08) were administered by tail vein injection 4 hours before PHx. The mice were humanly euthanized at indicated time after PHx. Blood and liver tissue samples were collected for examination. All animal experiments were approved by the Ethics Committee Medical College of Qingdao University (approval no. QDU-AEC-2021151).

巨噬細胞清除材料和方法文獻截圖：