Institute of Cancer Stem Cell, The First Affiliated Hospital, Dalian Medical University Cancer Center, Dalian, China; Department of Anatomy, Qiqihar Medical University, Qiqihar, China.
J Pineal Res. 2014 Nov;57(4):442-50. doi: 10.1111/jpi.12184. Epub 2014 Oct 14.
Hypoxia-induced inflammation and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Melatonin possesses anti-inflammatory and antiproliferative properties. However, the effect of melatonin on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 wk to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio, and median width of pulmonary arterioles. Melatonin attenuated the elevation of RVSP, RV/LV+S, and mitigated the pulmonary vascular structure remodeling. Melatonin also suppressed the hypoxia-induced high expression of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor-1α (HIF-1α), and nuclear factor-κB (NF-κB). In vitro, melatonin concentration-dependently inhibited the proliferation of PASMCs and the levels of phosphorylation of Akt and extracellular signal-regulated kinases1/2 (ERK1/2) caused by hypoxia. These results suggested that melatonin might potentially prevent HPH via anti-inflammatory and antiproliferative mechanisms.
低氧诱导的炎症和肺动脉平滑肌细胞（PASMCs）的过度增殖在低氧性肺动脉高压（HPH）的病理过程中起重要作用。褪黑素具有抗炎和抗增殖作用。然而，褪黑素对 HPH 的影响尚不清楚。在这项研究中，成年 Sprague-Dawley 大鼠暴露于间歇性慢性缺氧 4 周，以模拟严重的 HPH 情况。血流动力学和肺病理形态学数据显示，慢性缺氧显著增加右心室收缩压（RVSP）、右心室/左心室加室间隔（RV/LV+S）的重量比以及中肺动脉的中位数宽度。褪黑素减轻了 RVSP、RV/LV+S 的升高，并减轻了肺血管结构重塑。褪黑素还抑制了缺氧诱导的增殖细胞核抗原（PCNA）、缺氧诱导因子-1α（HIF-1α）和核因子-κB（NF-κB）的高表达。在体外，褪黑素浓度依赖性地抑制了 PASMCs 的增殖以及缺氧引起的 Akt 和细胞外信号调节激酶 1/2（ERK1/2）磷酸化水平。这些结果表明，褪黑素可能通过抗炎和抗增殖机制预防 HPH。
