中文摘要:
尽管最近取得了进展,但严重急性胰腺炎 (SAP) 仍然是一种致命的炎症,治疗选择有限。在这里,我们提供了令人信服的证据,证明 GV-971 (寡甘露酸钠) 是一种抗阿尔茨海默病药物,在各种雄性小鼠 SAP 模型中是一种保护剂。微生物组测序,以及肠道微生物群移植和质谱流式细胞术技术,揭示了 GV-971 重塑肠道微生物群,增加粪杆菌种群并调节外周和肠道免疫系统。对 GV-971 处理的 SAP 小鼠盲肠内容物的代谢组学分析进一步确定短链脂肪酸,包括丙酸盐和丁酸盐,是通过阻断 MAPK 通路抑制巨噬细胞 M1 极化和随后的致命炎症的关键代谢物。这些发现表明 GV-971 通过靶向微生物群代谢免疫轴是一种很有前途的 SAP 治疗方法。
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.
论文信息:
论文题目:GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis
期刊名称:Nature Communications
时间期卷:15, Article number: 8278 (2024)
在线时间:2024年9月27日
DOI:doi.org/10.1038/s41467-024-52398-z
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes and Control Liposomes
办事处:Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体助力急性胰腺炎模型研究,荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications:
氯膦酸盐脂质体ClodronateLiposomes助力急性胰腺炎模型巨噬细胞清除
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法:
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.