Song Ruolin, Broytman Oleg, Liang Nicole, Setzke Jonathan, Setzke Christopher, Wojdyla Gabriela, Pegelow David F, Osman Fauzia, Sorkness Ronald L, Watters Jyoti J, Teodorescu Mihaela
Department of Medicine, University of Wisconsin, Madison, WI, USA.
Department of Pediatrics, School of Medicine and Public Health,University of Wisconsin, Madison, WI, USA.
Respir Physiol Neurobiol. 2023 Jan;307:103982. doi: 10.1016/j.resp.2022.103982. Epub 2022 Nov 1.
Clinical case series suggest beneficial effects of low-dose intermittent hypoxia in asthma. We tested cardiopulmonary effects of repetitive acute hypoxic preconditioning (RAHP) during allergic inflammation. Brown Norway rats were sensitized to house dust mites (HDM) and exposed to 4-week RAHP or normoxia (SHAM), concurrent with weekly HDM or saline (SAL) challenges. We assessed methacholine responses and lung HIF-1α expression at endpoint, and weekly blood pressure (BP). RAHP relative to SHAM: 1) in HDM-challenged rats, showed no protection against HDM-induced airway dysfunction and did not significantly impact BP (week 4 mean BP difference = 10.51 mmHg, p = 0.09) or HIF-1α expression; 2) in SAL-challenged rats, attenuated airway responses to methacholine, reduced BP (week 4 mean BP average difference = -8.72 mmHg, p = 0.04) and amplified HIF-1α expression (p = 0.0086). Four weeks of RAHP did not mitigate the allergen-induced lower airway dysfunction and may detrimentally affect BP. However, it elicited beneficial cardiopulmonary responses in SAL-challenged rats, concurrent with increased HIF-1α expression.
临床病例系列研究表明，低剂量间歇性低氧对哮喘具有有益作用。我们测试了在过敏性炎症期间重复急性低氧预处理（RAHP）对心肺的影响。将棕色挪威大鼠对屋尘螨（HDM）进行致敏，并使其暴露于4周的RAHP或常氧环境（假手术组），同时每周用HDM或生理盐水（SAL）进行激发。我们在实验终点评估了乙酰甲胆碱反应和肺组织中缺氧诱导因子-1α（HIF-1α）的表达，并每周测量血压（BP）。与假手术组相比，RAHP：1）在HDM激发的大鼠中，对HDM诱导的气道功能障碍没有保护作用，对血压（第4周平均血压差异=10.51 mmHg，p=0.09）或HIF-1α表达也没有显著影响；2）在SAL激发的大鼠中，减弱了气道对乙酰甲胆碱的反应，降低了血压（第4周平均血压平均差异=-8.72 mmHg，p=0.04），并增强了HIF-1α的表达（p=0.0086）。4周的RAHP并不能减轻变应原诱导的下气道功能障碍，可能会对血压产生不利影响。然而，它在SAL激发的大鼠中引发了有益的心肺反应，同时HIF-1α表达增加。
