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通过miR-21/PTEN/AKT途径探索硼化合物在盲肠结扎和穿刺诱导的脓毒症中的抗炎活性。

Exploring the anti‑inflammatory activity of boron compounds through the miR‑21/PTEN/AKT pathway in cecal ligation and puncture‑induced sepsis.

作者信息

Sevim Çiğdem, Ozkaraca Mustafa, Kara Mehtap, Taghizadehghalehjoughi Ali, Genç Sidika, Yeni Yesim, Mendil Ali Sefa, Spanakis Marios, Ozcagli Eren, Kuzmin Sergey V, Spandidos Demetrios A, Tsatsakis Aristides

机构信息

Department of Medical Pharmacology, Faculty of Medicine, Kastamonu University, 37200 Kastamonu, Türkiye.

Department of Pathology, Faculty of Veterinary, Cumhuriyet University, 58070 Sivas, Türkiye.

出版信息

Mol Med Rep. 2025 Feb;31(2). doi: 10.3892/mmr.2024.13417. Epub 2024 Dec 20.

Abstract

The present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR‑21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑10, and gene expression of microRNA‑21 (miR‑21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR‑21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR‑21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low‑dose BA and BX in ameliorating sepsis‑induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.

摘要

本研究调查了硼酸(BA)和硼砂(BX)对经盲肠结扎和穿刺(CLP)诱导的脓毒症雄性Sprague Dawley大鼠肝脏和肾脏组织中炎症标志物以及miR-21/PTEN/AKT信号通路基因变化的影响。总共60只雄性Sprague Dawley大鼠被随机分为6组,每组10只动物,分组如下:对照组、CLP组(造模组)、20mg/kg BX组(CLP + BX1)、40mg/kg BX组(CLP + BX2)、20mg/kg BA组(CLP + BA1)和40mg/kg BA组(CLP + BA2)。对肝脏和肾脏组织进行组织病理学变化分析、肿瘤坏死因子-α、白细胞介素(IL)-6和IL-10的免疫阳性分析以及微小RNA-21(miR-21)、磷酸酶和张力蛋白同源物(PTEN)及AKT的基因表达分析。肝脏组织中的基因表达分析显示,CLP组中miR-21显著降低,PTEN水平显著但不明显降低,而CLP组中AKT表达显著增加,与CLP组相比,CLP + BA1组中AKT表达显著降低。在肾脏组织中,CLP组中miR-21水平显著降低,但与CLP组相比,CLP + BA2组中miR-21水平显著升高。这些结果表明低剂量BA和BX在改善脓毒症诱导的组织损伤方面具有潜在的治疗益处,强调需要进一步探索其作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/356f/11664231/e46eee04e9b7/mmr-31-02-13417-g00.jpg

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