氯膦酸鹽脂質(zhì)體ClodronateLiposomes助力急性胰腺炎模型巨噬細(xì)胞清除

中文摘要：

盡管最近取得了進(jìn)展，但嚴(yán)重急性胰腺炎 （SAP） 仍然是一種致命的炎癥，治療選擇有限。在這里，我們提供了令人信服的證據(jù)，證明 GV-971 （寡甘露酸鈉） 是一種抗阿爾茨海默病藥物，在各種雄性小鼠 SAP 模型中是一種保護(hù)劑。微生物組測序，以及腸道微生物群移植和質(zhì)譜流式細(xì)胞術(shù)技術(shù)，揭示了 GV-971 重塑腸道微生物群，增加糞桿菌種群并調(diào)節(jié)外周和腸道免疫系統(tǒng)。對 GV-971 處理的 SAP 小鼠盲腸內(nèi)容物的代謝組學(xué)分析進(jìn)一步確定短鏈脂肪酸，包括丙酸鹽和丁酸鹽，是通過阻斷 MAPK 通路抑制巨噬細(xì)胞 M1 極化和隨后的致命炎癥的關(guān)鍵代謝物。這些發(fā)現(xiàn)表明 GV-971 通過靶向微生物群代謝免疫軸是一種很有前途的 SAP 治療方法。

英文摘要：

Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.

論文信息：

論文題目：GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis

期刊名稱：Nature Communications

時間期卷：15, Article number: 8278 (2024)

在線時間：2024年9月27日

DOI：doi.org/10.1038/s41467-024-52398-z

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點科技）

Clodronate Liposomes氯膦酸鹽脂質(zhì)體助力急性胰腺炎模型研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：

氯膦酸鹽脂質(zhì)體ClodronateLiposomes助力急性胰腺炎模型巨噬細(xì)胞清除

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

Macrophage depletion

Mice were pre-treated with high-dose GV-971 for 7 days. On the sixth day, macrophages were either depleted by intraperitoneal injections of clodronate liposomes (CL, CP-005-005, Liposoma, Holland) or received PBS liposomes (PL, CP-005-005, Liposoma). On the eighth day, SAP was induced in the mice through 11 hourly injections of caerulein (50?μg/kg/hour) and a single dose of LPS (10?mg/kg). Euthanasia was performed, and relevant samples were collected from mice in the four groups 24?hours after SAP induction and subjected to the analysis of serum lipase and amylase and immunohistochemical staining.