肝臟再生模型里面,巨噬細胞如何發揮功能?一個重要的手段就是使用巨噬細胞清除氯膦酸鹽脂質體Clodronate Liposomes。金標準產品就是荷蘭Liposoma的CP-005-005。可以參考如下文獻。
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

肝臟切除前4h,尾靜脈注射清除劑C-005和對照試劑P-005。48h后取肝臟做免疫組化IHC,染色F4/80。IHC顯示,荷蘭Liposoma的CP-005-005巨噬細胞清除套裝,有效的清除了肝臟巨噬細胞。
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).
巨噬細胞清除會延緩肝臟再生進程,并抑制肝細胞增殖。


圖4.巨噬細胞清除會延緩肝臟再生與肝細胞增殖
(A) 本實驗中巨噬細胞清除聯合部分肝切除(PHx)體內造模流程示意圖。
(B) 對照組(NC)與巨噬細胞清除組(CLs)小鼠在 PHx 術后第 2 天肝臟組織 F4/80 抗原免疫組化(IHC)染色代表性圖片(比例尺,100 μm)。
(C) PHx 術后對照組與巨噬細胞清除組小鼠生存曲線(每組 n=10)。
(D) PHx 術后各時間點小鼠肝重 / 體重比(每組 n=4~6)。
(E) 肝臟組織切片中 Ki67 陽性、BrdU 陽性細胞免疫熒光(IF)染色代表性圖片(比例尺,100 μm)。
(F、G) 肝臟切片中 Ki67?、BrdU?細胞數量統計(每組 n=5)。
(H) PHx 術后 48 小時,對照組(NC)與巨噬細胞清除組(CLs)小鼠肝臟 CCND1、PCNA、前體半胱天冬酶 3(Pro-Cas3)、活化剪切型半胱天冬酶 3(C-Cas3)蛋白表達的蛋白質免疫印跡(Western blot)檢測結果(每組 n=4)。
(I、J) 末端脫氧核苷酸轉移酶介導的 dUTP 缺口末端標記(TUNEL)染色代表性圖片及陽性細胞定量統計(比例尺,100 μm)(每組 n=5)。