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腹腔内葡萄糖耐量试验、肺功能测量以及肺固定术,以研究肥胖和代谢受损对肺部结局的影响。

Intraperitoneal Glucose Tolerance Test, Measurement of Lung Function, and Fixation of the Lung to Study the Impact of Obesity and Impaired Metabolism on Pulmonary Outcomes.

作者信息

Dinger Katharina, Mohr Jasmine, Vohlen Christina, Hirani Dharmesh, Hucklenbruch-Rother Eva, Ensenauer Regina, Dötsch Jörg, Alejandre Alcazar Miguel A

机构信息

Translational Experimental Pediatrics, Experimental Pulmonology, Department of Pediatrics and Adolescent Medicine, University of Cologne.

Translational Experimental Pediatrics, Experimental Pulmonology, Department of Pediatrics and Adolescent Medicine, University of Cologne; Department of Pediatrics and Adolescent Medicine, University of Cologne.

出版信息

J Vis Exp. 2018 Mar 15(133):56685. doi: 10.3791/56685.

Abstract

Obesity and respiratory disorders are major health problems. Obesity is becoming an emerging epidemic with an expected number of over 1 billion obese individuals worldwide by 2030, thus representing a growing socioeconomic burden. Simultaneously, obesity-related comorbidities, including diabetes as well as heart and chronic lung diseases, are continuously on the rise. Although obesity has been associated with increased risk for asthma exacerbations, worsening of respiratory symptoms, and poor control, the functional role of obesity and perturbed metabolism in the pathogenesis of chronic lung disease is often underestimated, and underlying molecular mechanisms remain elusive. This article aims to present methods to assess the effect of obesity on metabolism, as well as lung structure and function. Here, we describe three techniques for mice studies: (1) assessment of intraperitoneal glucose tolerance (ipGTT) to analyze the effect of obesity on glucose metabolism; (2) measurement of airway resistance (Res) and respiratory system compliance (Cdyn) to analyze the effect of obesity on lung function; and (3) preparation and fixation of the lung for subsequent quantitative histological assessment. Obesity-related lung diseases are probably multifactorial, stemming from systemic inflammatory and metabolic dysregulation that potentially adversely influence lung function and the response to therapy. Therefore, a standardized methodology to study molecular mechanisms and the effect of novel treatments is essential.

摘要

肥胖和呼吸系统疾病是主要的健康问题。肥胖正成为一种新的流行疾病,预计到2030年全球肥胖人数将超过10亿,从而带来日益加重的社会经济负担。与此同时,包括糖尿病以及心脏和慢性肺部疾病在内的肥胖相关合并症也在持续增加。尽管肥胖与哮喘发作风险增加、呼吸道症状恶化及控制不佳有关,但肥胖和代谢紊乱在慢性肺病发病机制中的功能作用常常被低估,其潜在的分子机制仍不清楚。本文旨在介绍评估肥胖对代谢以及肺结构和功能影响的方法。在此,我们描述三种用于小鼠研究的技术:(1)评估腹腔内葡萄糖耐量(ipGTT)以分析肥胖对葡萄糖代谢的影响;(2)测量气道阻力(Res)和呼吸系统顺应性(Cdyn)以分析肥胖对肺功能的影响;(3)制备并固定肺以便随后进行定量组织学评估。肥胖相关的肺部疾病可能是多因素的,源于全身炎症和代谢失调,这可能对肺功能和治疗反应产生潜在的不利影响。因此,研究分子机制和新治疗方法效果的标准化方法至关重要。

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