Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
Medizinischen Klinik I, Universitätsklinikum RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Respir Res. 2020 Jun 3;21(1):136. doi: 10.1186/s12931-020-01394-0.
Obesity and pulmonary hypertension (PH) share common characteristics, such as augmented inflammation and oxidative stress. However, the exact role of obesity in the pathology of PH is largely uninvestigated. Therefore, we have hypothesized that in the context of obesity the gender difference may have influence on development of PH in animal models of this disease.
Animal experiments were conducted in monocrotaline (MCT) and chronic hypoxia (HOX) models of PH. Lean and obese Zucker rats or B6 mice of both genders were used for MCT or HOX models, respectively. Echocardiography, hemodynamic measurements, histology and immuno-histochemistry were performed to analyze various parameters, such as right ventricular function and hypertrophy, hemodynamics, pulmonary vascular remodeling and lung inflammation.
Both lean and obese male and female Zucker rats developed PH after a single MCT injection. However, negligible differences were seen between lean and obese male rats in terms of PH severity at the end stage of disease. Conversely, a more prominent and severe PH was observed in obese female rats compared to their lean counterparts. In contrast, HOX induced PH in lean and obese, male and female mice did not show any apparent differences.
Gender influences PH severity in obese MCT-injected rats. It is also an important factor associated with altered inflammation. However, further research is necessary to investigate and reveal the underlying mechanisms.
肥胖症和肺动脉高压（PH）具有共同的特征，如炎症和氧化应激增加。然而，肥胖症在 PH 病理中的确切作用在很大程度上尚未得到研究。因此，我们假设在肥胖症的背景下，性别差异可能会对这种疾病的动物模型中 PH 的发展产生影响。
在野百合碱（MCT）和慢性低氧（HOX）PH 模型中进行了动物实验。瘦和肥胖 Zucker 大鼠或两性的 B6 小鼠分别用于 MCT 或 HOX 模型。进行超声心动图、血流动力学测量、组织学和免疫组织化学分析各种参数，如右心室功能和肥大、血流动力学、肺血管重塑和肺炎症。
瘦和肥胖的雄性和雌性 Zucker 大鼠在单次 MCT 注射后均发展为 PH。然而，在疾病末期，瘦和肥胖雄性大鼠之间的 PH 严重程度几乎没有差异。相反，与瘦大鼠相比，肥胖雌性大鼠的 PH 更为明显和严重。相比之下，HOX 诱导的瘦和肥胖、雄性和雌性小鼠的 PH 没有显示出任何明显的差异。
性别影响肥胖 MCT 注射大鼠的 PH 严重程度。它也是与炎症改变相关的一个重要因素。然而，需要进一步研究以探讨和揭示潜在的机制。
