Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70

Abstract

HHP (hypobaric hypoxia preconditioning) induces the overexpression of HSP70 (heat-shock protein 70), as well as tolerance to cerebral ischaemia. In the present study, we hypothesized that HHP would protect against HAE (high-altitude exposure)-induced acute lung injury and oedema via promoting the expression of HSP70 in lungs prior to the onset of HAE. At 2 weeks after the start of HHP, animals were exposed to a simulated HAE of 6000 m in a hypobaric chamber for 24 h. Immediately after being returned to ambient pressure, the non-HHP animals had higher scores of alveolar oedema, neutrophil infiltration and haemorrhage, acute pleurisy (e.g. increased exudate volume, increased numbers of polymorphonuclear cells and increased lung myeloperoxidase activity), increased pro-inflammatory cytokines [e.g. TNF-α (tumour necrosis factor-α), IL (interleukin)-1β and IL-6], and increased cellular ischaemia (i.e. glutamate and lactate/pyruvate ratio) and oxidative damage [glycerol, NOx (combined nitrate+nitrite) and 2,3-dihydroxybenzoic acid] markers in the BALF (bronchoalveolar fluid). HHP, in addition to inducing overexpression of HSP70 in the lungs, significantly attenuated HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage in the lungs. The beneficial effects of HHP in preventing the occurrence of HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage was reduced significantly by pretreatment with a neutralizing anti-HSP70 antibody. In conclusion, HHP may attenuate the occurrence of pulmonary oedema, inflammation, and ischaemic and oxidative damage caused by HAE in part via up-regulating HSP70 in the lungs.

Establishment and evaluation of an experimental rat model for high-altitude intestinal barrier injury

“…The height limit for human survival is 5,000 m and 90% of humans live within an altitude range of 3,000–4,000 m. Thus, whether the environment at an altitude of 7,000 m induces a similar injury to an altitude of 4,000 m remains unclear. Furthermore, when producing a model at a simulated altitude of 7,000 m, the samples must be collected at an altitude <4,000 m. This may cause reperfusion injury or oxidative stress, which potentially differs from single acute hypoxia-induced intestinal injury (24). Based on previous preliminary studies (15,25), only acute hypoxia occurring at an altitude of 3,000–5,000 m does not cause injury.…”

Serum Heat Shock Protein Levels and the Relationship of Heat Shock Proteins with Various Parameters in Chronic Obstructive Pulmonary Disease Patients

“…there are a little data for the production of HSPs in the lung airway cells response to chronic hypoxia [29]. Increased HSP70 and HSP90 and unchanged HSP70 levels in lung tissue against chronic hypoxia were shown [29][30][31]. Consequently, the activation of heat shock response is important in stressresponsive pathways to long-term anoxic survival [32].…”

Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage

“…Reactive oxygen species (ROS) generated in a hypoxic heart will suppress myocardial contraction and induce cell damage and death [1,2]. At the molecular level, an increased generation of ROS will induce mitochondrial permeability transition pore (mPTP) opening, a loss of mitochondrial membrane potential, mitochondrial swelling and, ultimately, mitochondrial dysfunction [3,4]. A constant supply of O 2 is essential to sustaining cardiac function and viability [5].…”