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香芹酚可保护大鼠免受博来霉素诱导的肺氧化应激、炎症和纤维化。

Carvacrol protects rats against bleomycin-induced lung oxidative stress, inflammation, and fibrosis.

机构信息

Behbahan Faculty of Medical Sciences, Behbahan, Iran.

Department of Pharmacology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):10075-10089. doi: 10.1007/s00210-024-03273-7. Epub 2024 Jul 8.

Abstract

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-β1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

摘要

本研究的主要目的是研究香芹酚(CAR)在减轻博来霉素(BLM)诱导的肺纤维化(PF)中的潜在疗效。将 66 只雄性 Wistar 大鼠分为 7 天和 21 天两个主要组。它们被分为对照组、BLM 组、CAR80 组(仅用于 21 天组)和 CAR 治疗组。CAR 治疗组在气管内滴注 BLM(5mg/kg)后,分别给予 CAR(20、40 和 80mg/kg,口服)7 天或 21 天。结果表明,BLM 显著增加了支气管肺泡灌洗液中的总细胞计数和中性粒细胞和淋巴细胞的百分比,降低了巨噬细胞的百分比。CAR 呈剂量依赖性地降低了总细胞计数和中性粒细胞和淋巴细胞的百分比。CAR 显著降低了博来霉素暴露大鼠的丙二醛反应物质和羟脯氨酸水平,并提高了总巯基水平和过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。此外,CAR 在第 7 天和第 21 天降低了转化生长因子-β1、结缔组织转化生长因子和肿瘤坏死因子-α的水平。BLM 在第 7 天增加了干扰素-γ的水平,但在第 21 天降低了其水平。然而,CAR 在第 7 天和第 21 天逆转了干扰素-γ的水平。根据组织病理学发现,BLM 在第 7 天和第 21 天引起炎症,但对于纤维化的诱导,21 天的研究显示出比 7 天组更多的纤维化损伤。CAR 显示出对纤维化损伤的改善。CAR 对 BLM 诱导的肺纤维化的作用可能与其抗氧化、抗炎和抗纤维化活性有关。

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