Investigation of airway inflammation and asthma by repeated bronchoalveolar lavage combined with measurements of airway and lung tissue mechanics in individual rats.
Acute and chronic airway inflammations are the main pathogenetic features of numerous pulmonary diseases. There are several methods studying the pathomechanisms of inflammatory respiratory diseases. To asses the severity of lung diseases, the bronchoalveolar lavage (BAL) and lung function tests are...
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| Dokumentumtípus: | Disszertáció |
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2011-06-21
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| doi: | 10.14232/phd.709 |
| mtmt: | 2770688 |
| Online Access: | http://doktori.ek.szte.hu/709 |
| Tartalmi kivonat: | Acute and chronic airway inflammations are the main pathogenetic features of numerous pulmonary diseases. There are several methods studying the pathomechanisms of inflammatory respiratory diseases. To asses the severity of lung diseases, the bronchoalveolar lavage (BAL) and lung function tests are the most current diagnostic methods in the experimental and human pulmonology. However, repetition of BAL procedures and assessments of respiratory mechanic parameters in small rodents (mice and rats) mostly are not allowed, animals are regularly sacrificed at the end of the experiments. For that reason there is no possibility for serial assessments, longitudinal follow-up of pathological changes and comparison of results within the same animals. In present study there is exhibited an individual animal model that provides follow-up of bronchoalveolar lavage fluid (BALF) with analysis of cellular profile, as well as the respiratory mechanics by methods of reproducible, partial BALF collections and separately measured airways and lung tissue mechanics with low frequency forced oscillation technique (FOT) in individual rats. Longitudinal changes are detected within the same animals in BALF cellular profile and lung tissue mechanics by induction of an acute lung injury (ALI) with an intraperitoneal injection of E coli lipopolysaccharide (LPS). Bronchial hyperreactivity (BHR) to exogenous constrictor stimuli (metacholin) are assessed and the influx of cells into the lungs repeatedly in rats exposed to different modes of administration of the allergen, ovalbumin (OVA). Furthermore, histopathological consequences of lung tissue followed by LPS and OVA expositions are identified. The applied method allows longitudinal follow-up of the BALF cellular profile and airway and lung tissue mechanics in rats. Subsequent systemic administration of LPS, makes the early detection of ALI possible in the BALF and respiratory mechanics. Following single systemic administration combined with chronic inhalation of OVA, the self-controlled study design provides experimental evidence of the strong association between the BHR and the number of eosinophils in the BALF. On the basis of histopathological results, the LPS induced rat model is not only suitable for the investigation of ALI/ARDS, but also allows an assessment of a chronic inflammatory process leading to bronchus associated lung tissue (BALT) hyperplasia and emphysaema. Furthermore, following the OVA sensitisation a chronic inflammation with allergic characterisation is revealed in the rat lung tissue. In conclusion, these animal models may be feasible to research of experimental ALI/ARDS, BALT, emphysaema and asthma bronchiale. |
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