Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, P.R. China.
Scientific Research Center, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, P.R. China.
PLoS One. 2018 Apr 11;13(4):e0195604. doi: 10.1371/journal.pone.0195604. eCollection 2018.
Endothelial dysfunction is one of the main pathological changes in Obstructive sleep apnoea (OSA). The Rho kinase (ROCK) pathway is associated with endothelial dysfunction. However, the interaction between ROCK and nuclear factor of activated T cells isoform c3 (NFATc3) in the development of this pathological response under chronic intermittent hypoxia (CIH) is unclear. To simulate the OSA model, we established a moderate CIH rat model by administering the fraction of inspired O2 (FiO2) from 21% to 9%, 20 times/h, 8 h/day for 3 weeks. Fasudil (ROCK inhibitor, 8 mg/kg/d, i.p.) was administrated in the rats exposed to CIH for 3 weeks. Our results demonstrated that CIH caused significantly endothelial dysfunction, accompanying with increased ET-1 level, decreased eNOS expression and NO production, which reduced ACh-induced vascular relaxation responses. Moreover, RhoA/ROCK-2/NFATc3 expressions were up-regulated. Fasudil significantly improved CIH induced endothelial dysfunction. Data suggested that the ROCK activation is necessary for endothelial dysfunction during CIH.
内皮功能障碍是阻塞性睡眠呼吸暂停（OSA）的主要病理变化之一。Rho 激酶（ROCK）途径与内皮功能障碍有关。然而，在慢性间歇性低氧（CIH）下，ROCK 与激活 T 细胞核因子 c3 同种型（NFATc3）之间的相互作用在这种病理反应的发展中尚不清楚。为了模拟 OSA 模型，我们通过给予吸入氧气分数（FiO2）从 21%降至 9%，20 次/小时，每天 8 小时，持续 3 周，建立了中度 CIH 大鼠模型。在暴露于 CIH 的大鼠中，给予法舒地尔（ROCK 抑制剂，8mg/kg/d，腹腔注射）3 周。我们的结果表明，CIH 导致明显的内皮功能障碍，伴随着 ET-1 水平升高、eNOS 表达和 NO 产生减少，从而降低了 ACh 诱导的血管舒张反应。此外，RhoA/ROCK-2/NFATc3 的表达上调。法舒地尔显著改善了 CIH 引起的内皮功能障碍。数据表明，在 CIH 期间 ROCK 激活对于内皮功能障碍是必要的。
