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去分化脂肪细胞给药可改善实验性坏死性小肠结肠炎中脂肪酸代谢相关蛋白表达异常和肠组织损伤。

Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis.

机构信息

Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan.

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Sci Rep. 2023 May 22;13(1):8266. doi: 10.1038/s41598-023-34156-1.

Abstract

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C-C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation.

摘要

新生儿坏死性小肠结肠炎(NEC)是一种严重的早产儿疾病,需要重症监护,经常导致危及生命的并发症和高死亡率。去分化脂肪细胞(DFATs)是从成熟脂肪细胞衍生而来的间充质干细胞样细胞。将 DFATs 腹腔内给予 NEC 大鼠模型,并评估其治疗效果及其机制。使用人工乳喂养的大鼠幼仔建立 NEC 模型,使其经历窒息和冷应激,并在剖宫产术后给予口服脂多糖。在出生后 96 小时处死幼仔进行宏观组织学检查和蛋白质组学分析。DFATs 给药可显著提高存活率,从 25.0%(载体组)提高至 60.6%(DFAT 组),与载体组相比,宏观、组织学和细胞凋亡评估显著降低。此外,CC 基序趋化因子 2 的表达显著降低,DFAT 组白细胞介素 6 的表达降低。DFAT 给药改善了 93 种主要与 NEC 上调/下调的 436 种蛋白质中的脂肪酸代谢蛋白相关的蛋白质。DFATs 改善了 NEC 中的死亡率和受损的肠道组织,可能是通过改善异常的脂肪酸相关蛋白表达和减轻炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faa8/10203254/b1d538542d14/41598_2023_34156_Fig1_HTML.jpg

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