Degree of brain, lung and heart tissues pathology injury is strongly related to the hypoxia altitude and duration. Morphologically, the degree of the brain, lung and heart tissues damage was aggravated after the difference hypoxia. Positive correlations were found between the degree of the brain, lung and heart damage and the hypoxia altitude and duration, meanwhile, HIF-1α showed an increasing trend as the altitude of hypoxia increased and the duration of hypoxia increased.
In the state of hypoxia, the pathological damage of brain and lung tissue is more serious than that of myocardial tissue. It may be because the sensitivity of myocardial tissue is not higher than in brain and lung tissue when the individual acute exposed to plateau. Whereas a recent report by Li showed that myocardial tissue damage was aggravated with the prolongation of exposure to hypoxia after 3 d, 7 d, 15 d, and 30 d. It was observed that the arrangement of myocardial cells was disordered, the boundary of muscle fibers was blurred, and inflammatory cells infiltrated (18). In Li's study, the hypoxia duration of the rats was at least 72 h but the hypoxia duration of cardiomyocytes in our experiment was at most 72 h, suggesting that the heart should be considered for the hypoxia tolerance in the late-stage study.
This process is currently considered to be produced at the cellular level endogenous protective mechanism. Between different organs of the mechanism of hypoxic acclimatization have not the same. Elevation of HIF-1α at the early terms after hypoxic exposure established in rats seems to promote rapid and more effective adaptation of these rats to hypoxia.
This is a “productivity system” when the rapid degradation of HIF-1α and the stability regulation of its transcriptional activity for rapid perceptive response to hypoxic. In our results, a complex HIF “switch” mechanism to regulate the cellular or whatever responded to hypoxia with specific altitudinal and temporal roles. Different hypoxia altitude and duration tests showed that the expression of HIF-1α emerged an upward trend along with altitude and duration. When stand in the middle and low altitude region for a short time, the organism has an adaption to the hypoxic via mobilizing HIF-1α to activate many hundreds of target genes in the signal pathway (19), meanwhile, HIF-1α is in dynamic equilibrium on the account of continuously entering the nuclear transcription and translation on the one hand, on the other hand continuously degrading by PHD or others recognition simultaneously, now HIF-1α is a beneficial signal factor for the body. Nevertheless, when stay at high altitude for long-term, the dynamic balance of HIF-1α is destroyed assuming that the synthesize rate is greater than the degradation rate. Excrescent HIF-1α causes hyperirritable target genes reaching the peak of the physical performance, thereby multiple negative impacts damaging the tissue cells, destroying the cell structure and growth. At this moment, HIF-1α has become a harmful signal factor to the body.
Now that HIF-1α is a production at the cellular level against hypoxic exists in the animal brain, heart, liver and other tissues, organs and cells, which can increase the tolerance to hypoxia. Going higher, oxygen needs to be transported preferably to the life-sustaining organs: brain, heart, and lungs. An increase of HIF-1α, with the increase of altitude and duration, is a double-edged sword for organizations such as the brain.
Brain is a type of high oxygen consumption organs. Despite it constitutes only 2% of total body weight, it accounts for about 20% of whole O2 consumption. Furthermore, brain is characterized by high energy consumption and low energy reserve, particularly susceptible to hypoxic conditions (20). As a consequence, the brain is extremely sensitive to hypoxia. So when people during the rapid ascent to high altitudes, likely lead to the High-altitude cerebral edema (HACE) which is a life-threatening illness (21). HIF-1α expression enhanced the hypoxia adaptation capability of the rat through the regulation of expression of multiple genes. According to our findings, these experiments showed an increased expression of HIF-1α by hypoxic of altitude and duration increased.
As well, the lung is also responsible for oxygen uptake and the pulmonary vascular responses that ensure adequate blood flow to the alveoli in response to low oxygen tensions but likely results in pulmonary hypertension (PH) under chronic hypoxic (22). HAPE is induced by the high altitude hypoxia, a serious life-threatening acute mountain sickness, their common characteristics as pulmonary hypertension and vascular permeability changes, and prolonged exposure to alveolar hypoxia (due to chronic lung disease or residence at high altitude) is a significant cause of pulmonary hypertension (23).The results suggest that in lung tissue with low expression under normoxia HIF-1α, along with raising the level of hypoxic of altitude and duration, HIF-1α expression level gradually increased, indicating that HIF-lα in the regulation of hypoxic acclimatization process. To understand the precise role of the HIF system in lung development and in lung diseases such as pulmonary hypertension and HAPE, and the identification and creation of tools to manipulate HIF levels in vivo, hold promise for better therapeutic options to treat lung diseases caused by high altitude.
With exposure to hypoxia, the cardiac output and heart rate rise acutely (24), however, acute altitude exposure may trigger serious cardiovascular adverse events in subjects at risk (25). In our study, analysis of HIF-1α protein level in the rat heart, the results showed a slight difference between the normoxic group and hypoxic rats. When compared with normoxic group, HIF-1α protein level slightly increases in hypoxia group. The highest level of HIF-1α protein is seen in the hypoxia group at 8000 m and hypoxia for 72 hours group. Hypoxia induces gradual upregulation of HIF-1α, which in turn induces the expression of adaptive genes erythropoiesis, vascular endothelial growth factor, glucose transporter-1, nitric oxide synthase (26, 27). This means that there is an increase in HIF-1α protein level in hypoxic conditions and systemic adaptation occurs gradually at the cellular level in hypoxic conditions (27). The increase is thought to occur because tissues begin to adapt to hypoxic conditions.