研究动态
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在大鼠体内,TNF-α和IL-8水平与低压低氧性肺动脉高压和肺血管重建呈正相关。

TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats.

发表日期:2023
作者: Haixia Shi, Yongfeng Zhao, Su Li, Haitao Wu, Dehua Ma, Chenchen Wan
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

高原性肺动脉高压(PAH)中促炎细胞因子的表达状况已经得到了广泛的研究。然而,在从低压低氧环境脱离后的PAH中肺血管重塑(PVR)的可逆变化过程中,白细胞介素(IL)-8和肿瘤坏死因子α(TNF-α)的变化尚未阐明。本研究采用高原性PAH大鼠模型进行了研究。然后,高原组的PAH大鼠保持在高原地区,而低原组的大鼠返回到低原地区。进行0、10、20和30天PAH建模后,评估右室收缩压(RVSP)和平均肺动脉压(mPAP)。右室(RV)肥厚通过RV / [左室 + 心室间隔(S)]的比例来反映。血液呈现病理变化通过苏木精-伊红染色进行评估,并测量介质厚度(WT%)和介质面积(WA%)。用Western blot法和酶联免疫吸附法分别测定肺动脉组织和血液中的TNF-α和IL-8水平。我们的结果显示,PAH大鼠表现出明显增加的RVSP和mPAP,RV肥厚,PVR和TNF-α和IL-8的增强产生。然后,我们发现这些病理变化在高原组的大鼠体内逐渐加重,而TNF-α和IL-8水平在PAH建模的10、20和30天后也有所增加。相反,低原组的大鼠mPAP降低,PVR得到缓解,伴随着TNF-α和IL-8产量的减少。总之,我们的研究表明,在脱离低压低氧环境后,TNF-α和IL-8的产生也是可逆的,与PVR的严重程度呈正相关。© 2023年作者出版,由德古意特出版。
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.© 2023 the author(s), published by De Gruyter.