Bale Swarna, Sunkoju Manoj, Reddy Shiva Shankar, Swamy Veerabhadra, Godugu Chandraiah
Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Indian J Pharmacol. 2016 Nov-Dec;48(6):643-648. doi: 10.4103/0253-7613.194859.
Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain.
Mice were divided into two groups, BLM-treated and normal control. BLM via OPA (2 IU/kg) was used to induce PF. Water for injection was used as a vehicle in control animals. Body weights were measured once in a week, and the study was continued for 21 days. At the end of the study, animals were euthanized and bronchoalveolar lavage fluid was collected and subjected to lymphocytes count, estimation of albumin and protein levels. Lung tissues were collected, and various biochemical assays (malondialdehyde, glutathione, nitric oxide, hydroxyproline) and molecular techniques including ELISA and Western blot were performed to investigate the effect of OPA-BLM. Further, histopathology and Masson's trichrome staining techniques were performed in lung sections.
OPA administration of BLM in Swiss mice significantly induced PF, evident from lung index and morphology. Several oxidative stress parameters and hydroxyproline assay revealed the significant ( < 0.05) induction of PF. Further results obtained from histopathology, Masson's trichrome staining, ELISA, and Western blot confirmed the significant induction of PF via OPA-BLM.
BLM administration by OPA route in Swiss mice can be used as a simple, homogeneous, and noninvasive model of inducing PF and to investigate the effect of various anti-fibrotic agents as an alternative to IT-BLM.
肺纤维化（PF）是几种间质性肺病的一种进行性且主要致命的形式，目前治疗方法有限；因此，开发一种简单、同质且非侵入性的疾病模型以研究可能的抗纤维化方法至关重要。本研究旨在建立博来霉素（BLM）诱导的PF的口咽吸入（OPA）模型，作为在瑞士小鼠品系中气管内（IT）给予BLM的一种简单替代方法。
将小鼠分为两组，即BLM处理组和正常对照组。通过OPA给予BLM（2 IU/kg）以诱导PF。注射用水用作对照动物的载体。每周测量一次体重，研究持续21天。在研究结束时，对动物实施安乐死，收集支气管肺泡灌洗液并进行淋巴细胞计数、白蛋白和蛋白质水平的测定。收集肺组织，进行各种生化检测（丙二醛、谷胱甘肽、一氧化氮、羟脯氨酸）以及包括酶联免疫吸附测定（ELISA）和蛋白质印迹法在内的分子技术检测，以研究OPA-BLM的作用效果。此外，对肺切片进行组织病理学和Masson三色染色技术检测。
在瑞士小鼠中通过OPA给予BLM可显著诱导PF，这从肺指数和形态学上可以明显看出。多个氧化应激参数和羟脯氨酸检测显示PF诱导显著（<0.05）。从组织病理学、Masson三色染色、ELISA和蛋白质印迹法获得的进一步结果证实了通过OPA-BLM可显著诱导PF。
在瑞士小鼠中通过OPA途径给予BLM可作为一种简单、同质且非侵入性的诱导PF的模型，并作为IT-BLM的替代方法用于研究各种抗纤维化药物的作用效果。
