Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, No.201, Hubin Nan Road, Siming District, Xiamen, 361004, Fujian Province, People's Republic of China.
Teaching Hospital of Fujian Medical University, Xiamen, China.
Sleep Breath. 2019 Mar;23(1):341-348. doi: 10.1007/s11325-018-1720-9. Epub 2018 Sep 15.
Obstructive sleep apnea (OSA) is associated with renal impairs. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis and autophagy. The present study aims to evaluate the effect of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of OSA.
Mice were randomly allocated to normoxia, CIH, and CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12 weeks. Mice in the CIH+telmisartan group received telmisartan administration. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax and cleaved caspase-3 were conducted for evaluating apoptosis in kidney tissue. While the autophagy-related proteins, beclin-1 and LC3, were also observed via western blotting.
The percentage of apoptotic cell in the CIH group was significantly higher than that of normoxia group; meanwhile, Bax and cleaved caspase-3 protein levels were increased in the CIH group than those of normoxia group (all p < 0.05). Compared with the normoxia group, mice in the CIH group had greater autophagy-related proteins (beclin-1 and LC3) expression. When compared to the CIH group, both the renal apoptosis and autophagy in the CIH+telmisartan group were decreased.
The CIH accelerates renal apoptosis and autophagy levels. Telmisartan ameliorating those levels suggests that it might prevent renal impairs from the CIH in OSA patients.
阻塞性睡眠呼吸暂停（OSA）与肾脏损害有关。作为 OSA 的一种新的病理生理标志，慢性间歇性低氧（CIH）增强细胞凋亡和自噬。本研究旨在评估替米沙坦对 OSA 小鼠模型中 CIH 诱导的肾脏细胞凋亡和自噬的影响。
将小鼠随机分为常氧组、CIH 组和 CIH+替米沙坦组（每组 12 只）。CIH 暴露时间为 12 周。CIH+替米沙坦组给予替米沙坦给药。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）检测和 Bax 和 cleaved caspase-3 的 Western blot 检测评估肾脏组织中的细胞凋亡。同时通过 Western blot 观察自噬相关蛋白 beclin-1 和 LC3。
CIH 组的凋亡细胞百分比明显高于常氧组；同时，CIH 组的 Bax 和 cleaved caspase-3 蛋白水平高于常氧组（均 p<0.05）。与常氧组相比，CIH 组的自噬相关蛋白（beclin-1 和 LC3）表达增加。与 CIH 组相比，CIH+替米沙坦组的肾细胞凋亡和自噬均减少。
CIH 加速了肾脏细胞凋亡和自噬水平。替米沙坦改善这些水平表明，它可能预防 OSA 患者 CIH 引起的肾脏损害。
