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白藜芦醇减轻博来霉素诱导的大鼠肺损伤。

Resveratrol alleviates bleomycin-induced lung injury in rats.

作者信息

Sener Göksel, Topaloğlu Nurhayat, Sehirli A Ozer, Ercan Feriha, Gedik Nursal

机构信息

Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.

出版信息

Pulm Pharmacol Ther. 2007;20(6):642-9. doi: 10.1016/j.pupt.2006.07.003. Epub 2006 Sep 3.

Abstract

Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study was designed to examine the effects of resveratrol, an antioxidant agents, against bleomycin-induced pulmonary fibrosis and oxidative damage. Wistar albino rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) followed by either saline or resveratrol (10 mg/kg; orally) for 14 days. The effect of resveratrol on pulmonary oxidative damage was studied by cell count and analysis of cytokine levels (TGF-beta, TNF-alpha, IL-1beta and IL-6) in the bronchoalveolar lavage fluid (BALF) and biochemical measurements of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the lung tissue. Bleomycin-induced lung fibrosis was determined by lung collagen contents and also microscopically. Bleomycin caused a significant decrease in lung GSH, which was accompanied with significant increases in MDA level, MPO activity, and collagen contents of the lung tissue concomitant with increased levels of the pro-inflammatory mediators and cell count in BALF. On the other hand, resveratrol treatment reversed all these biochemical indices as well as histopathological alterations induced by bleomycin. The results demonstrate the role of oxidative mechanisms in bleomycin-induced pulmonary fibrosis, and resveratrol, by its antioxidant properties, ameliorates oxidative injury and fibrosis due to bleomycin. Thus, an effective supplement with resveratrol as an adjuvant therapy may be a very promising agent in alleviating the side effects of bleomycin, an effective chemotherapeutic agent.

摘要

抗氧化疗法可能对氧化-抗氧化平衡受损的疾病(如肺纤维化)有用。本研究旨在探讨抗氧化剂白藜芦醇对博来霉素诱导的肺纤维化和氧化损伤的影响。给Wistar白化大鼠单次气管插管注射博来霉素(5mg/kg),随后分别给予生理盐水或白藜芦醇(10mg/kg,口服),持续14天。通过细胞计数、支气管肺泡灌洗液(BALF)中细胞因子水平(转化生长因子-β、肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6)分析以及肺组织中脂质过氧化终产物丙二醛(MDA)、关键抗氧化剂谷胱甘肽(GSH)的生化测定和中性粒细胞浸润指标髓过氧化物酶(MPO)活性,研究白藜芦醇对肺氧化损伤的影响。通过肺胶原蛋白含量及显微镜检查确定博来霉素诱导的肺纤维化。博来霉素导致肺GSH显著降低,同时肺组织MDA水平、MPO活性和胶原蛋白含量显著增加,伴随BALF中促炎介质水平升高和细胞计数增加。另一方面,白藜芦醇治疗逆转了所有这些生化指标以及博来霉素诱导的组织病理学改变。结果表明氧化机制在博来霉素诱导的肺纤维化中起作用,白藜芦醇凭借其抗氧化特性改善了博来霉素引起的氧化损伤和纤维化。因此,作为辅助治疗有效补充白藜芦醇可能是减轻有效化疗药物博来霉素副作用的非常有前景的药物。

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