Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Physiol Res. 2023 Dec 29;72(S5):S499-S508. doi: 10.33549/physiolres.935218.
Sex seems to be a contributing factor in the pathogenesis of bronchial asthma. This study aimed to find sex-related differences in metabolome measured by hydrogen-1 nuclear magnetic resonance ((1)H NMR) spectroscopy in healthy and ovalbumin (OVA)-sensitized guinea pigs. Adult male and female animals were divided into controls and OVA-sensitized groups. OVA-sensitization was performed by OVA systemic and inhalational administration within 14 days; on day 15, animals were killed by anesthetic overdose followed by exsanguination. Blood was taken and differential white blood cell count was measured. Left lung was saline-lavaged and differential cell count in the bronchoalveolar lavage fluid (BALF) was measured. After blood centrifugation, plasma was processed for (1)H NMR analysis. Metabolomic data was evaluated by principal component analysis (PCA). Eosinophil counts elevated in the BALF confirming eosinophil-mediated inflammation in OVA-sensitized animals of both sexes. Sex differences for lactate, glucose, and citrate were found in controls, where these parameters were lower in males than in females. In OVA-sensitized males higher glucose and lower pyruvate were found compared to controls. OVA-sensitized females showed lower lactate, glucose, alanine, 3-hydroxy-butyrate, creatine, pyruvate, and succinate concentrations compared to controls. In OVA-sensitized animals, lactate concentration was lower in males. Data from females (healthy and OVA-sensitized) were generally more heterogeneous. Significant sex differences in plasma concentrations of metabolites were found in both healthy and OVA-sensitized animals suggesting that sex may influence the metabolism and may thereby contribute to different clinical picture of asthma in males and females.
性别似乎是支气管哮喘发病机制的一个影响因素。本研究旨在通过氢-1 核磁共振波谱((1)H NMR)技术,寻找健康和卵清蛋白(OVA)致敏豚鼠代谢组学中与性别相关的差异。成年雄性和雌性动物分为对照组和 OVA 致敏组。通过 OVA 全身和吸入给药在 14 天内进行 OVA 致敏;第 15 天,动物通过过量麻醉处死并放血。采集血液并进行白细胞分类计数。用生理盐水灌洗左肺,测量支气管肺泡灌洗液(BALF)中的细胞分类计数。血液离心后,处理血浆进行(1)H NMR 分析。采用主成分分析(PCA)对代谢组学数据进行评估。BALF 中的嗜酸性粒细胞计数升高证实了两性 OVA 致敏动物中嗜酸性粒细胞介导的炎症。在对照组中发现了性别差异的乳酸盐、葡萄糖和柠檬酸,其中这些参数在雄性中低于雌性。与对照组相比,OVA 致敏雄性中葡萄糖升高而丙酮酸降低。与对照组相比,OVA 致敏雌性中乳酸盐、葡萄糖、丙氨酸、3-羟基丁酸、肌酸、丙酮酸和琥珀酸盐浓度降低。在 OVA 致敏动物中,雄性的乳酸盐浓度较低。来自女性(健康和 OVA 致敏)的数据通常更具异质性。在健康和 OVA 致敏动物中均发现了代谢物血浆浓度的显著性别差异,这表明性别可能影响代谢,从而可能导致男性和女性哮喘的不同临床表现。