Shi Haixia, Zhao Yongfeng, Li Su, Wu Haitao, Ma Dehua, Wan Chenchen
Department of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, China.
Open Life Sci. 2023 Jul 27;18(1):20220650. doi: 10.1515/biol-2022-0650. eCollection 2023.
The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity.
促炎细胞因子在高原肺动脉高压（PAH）中的表达状况已得到充分研究。然而，脱离低压低氧环境后，PAH患者肺血管重塑（PVR）可逆性变化过程中白细胞介素（IL）-8和肿瘤坏死因子α（TNF-α）的变化尚未阐明。本研究建立了高原PAH大鼠模型。然后，将高原组的PAH大鼠置于高原地区饲养，低海拔组的大鼠返回低海拔地区。在PAH建模0、10、20和30天后，评估右心室收缩压（RVSP）和平均肺动脉压（mPAP）。右心室（RV）肥厚通过RV/[左心室+室间隔（S）]的比值反映。通过苏木精-伊红染色观察PVR的病理变化，并测量中膜厚度（WT%）和中膜面积（WA%）。分别采用蛋白质印迹法和酶联免疫吸附测定法检测肺动脉组织和血液中TNF-α和IL-8水平。我们的结果显示，PAH大鼠的RVSP和mPAP显著升高，出现RV肥厚、PVR，且TNF-α和IL-8生成增加。然后，我们发现这些病理变化在PAH建模10、20和30天后在高原组大鼠中逐渐加重，TNF-α和IL-8水平升高。相比之下，低海拔组大鼠的mPAP降低，PVR减轻，同时TNF-α和IL-8生成减少。总之，我们的研究表明，在脱离低压低氧环境后PVR的可逆性变化过程中，TNF-α和IL-8的生成也是可逆的。因此，促炎细胞因子TNF-α和IL-8水平与PVR严重程度呈正相关。
