Department of Cardial Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7573-7581. doi: 10.26355/eurrev_201909_18878.
The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism.
24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats.
Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-β, TNF-α, IL-1β, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1β, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group.
Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.
本研究建立大鼠肺动脉高压（PAH）模型，旨在阐明肝源性抗菌肽（Hepcidin）在 PAH 大鼠中的保护作用及其机制。
将 24 只雄性 Sprague Dawley（SD）大鼠随机分为假手术组、PAH 组和 Hepcidin 组，每组 8 只。动物手术后，测定大鼠血流动力学参数和右心室肥厚指数。酶联免疫吸附试验（ELISA）检测大鼠血清细胞因子。苏木精和伊红（H&E）染色观察肺组织病理损伤。最后，采用 Western blot 检测大鼠肺组织核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、血管细胞间黏附分子 1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和单核细胞趋化蛋白-1（MCP-1）的蛋白表达。
与假手术组相比，PAH 组大鼠平均肺动脉压（mPAP）和右心室收缩压（RVSP）明显升高（p<0.05）；而 Hepcidin 组大鼠的 mPAP 和 RVSP 均明显低于 PAH 组（p<0.05）。Hepcidin 治疗可减轻 PAH 大鼠肺组织的病理损伤。ELISA 结果表明，Hepcidin 治疗可显著降低 TGF-β、TNF-α、IL-1β和 IL-6 水平。此外，Western blot 结果显示，Hepcidin 组大鼠 NF-κB、TNF-α、IL-1β、VCAM-1、ICAM-1 和 MCP-1 的蛋白水平明显低于 PAH 组。
Hepcidin 通过抑制 NF-κB/TNF-α 通路减轻 PAH 大鼠的炎症反应。
