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采用 NNK 和高脂肪饮食相结合的非手术方法诱导 Wistar 大鼠肺癌。

A non-surgical method for induction of lung cancer in Wistar rats using a combination of NNK and high dietary fats.

机构信息

Department of Biotechnology, Hamdard University, Hamdard Nagar, New Delhi 110062, India.

出版信息

Protoplasma. 2013 Aug;250(4):919-29. doi: 10.1007/s00709-012-0478-3. Epub 2013 Jan 13.

Abstract

Lung cancer is one of the most common malignant neoplasms all over the world. Smoking and a number of constituents of tobacco are responsible for development of lung tumours; however, the deleterious effects of tobacco-derived carcinogen, nitrosamine 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone (NNK)) remain unmatched. We report the development of a novel rodent model by administering multiple doses of NNK to male Wistar rats and feeding them with high-fat and low-protein diet. Tumour cells in lungs were observed in approximately 98 % rats after 8 months of NNK treatment, as evident by histopathological analysis. This rodent model showed slow progression of lung tumours which has helped us to assess early indicators of oxidative damage in lungs by studying the levels of lipid peroxidation and antioxidant parameters. LPO was elevated by 46.94 %, SOD, CAT, GSH and GR activity was decreased by 48.67 %, 22.04 %, 21.46 % and 20.85 %, respectively in serum of NNK treated rats when compared with control. These findings suggest that increased oxidative stress can represent a risk factor for the development of chronic disease in early future. This new animal model is an attempt to greatly facilitate studies of the pathophysiology, biochemistry and therapy of lung cancer.

摘要

肺癌是全世界最常见的恶性肿瘤之一。吸烟和烟草中的一些成分是导致肺癌发生的原因;然而,烟草衍生的致癌物质亚硝胺 4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮(尼古丁衍生的亚硝胺酮(NNK))的有害影响仍然无法比拟。我们通过给雄性 Wistar 大鼠多次给予 NNK 并给它们喂食高脂肪和低蛋白饮食,开发了一种新型的啮齿动物模型。在 NNK 治疗 8 个月后,通过组织病理学分析,大约 98%的大鼠肺部观察到肿瘤细胞。这种啮齿动物模型显示肺癌的进展缓慢,这有助于我们通过研究脂质过氧化和抗氧化参数水平来评估肺部氧化损伤的早期指标。与对照组相比,NNK 处理大鼠血清中的 LPO 升高了 46.94%,SOD、CAT、GSH 和 GR 活性分别降低了 48.67%、22.04%、21.46%和 20.85%。这些发现表明,氧化应激的增加可能代表未来慢性疾病发展的一个风险因素。这种新的动物模型旨在极大地促进肺癌的病理生理学、生物化学和治疗研究。

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