Preliminary Study Of The Mechanisms Of Reduced Rats’ Physical Performance In Acute Hypoxia

Background:There is a significantly reduction in lowlanders’ physical performance when exposed tohigh altitude environment. Finding the key point that limit physical performance in highaltitude and subsequently figuring out a medical method to promote our troops’ militaryperformance is the most important thing in our military medical research.Exercise is regulated subtly by our body. Exercise fatigue was defined as one cannotmaintain the original exercise intensity after a period time of exercise. It can result from twopart of the body. One results from peripheral organs (which include spinal motor nerves,neuromuscular junction and skeletal muscle), is called peripheral fatigue; the other resultsfrom central nervous system (which include encephalon and spinal cord), is called centralfatigue. Because hypoxia (lacking of oxygen in body) is the most important factor that affectshuman body in high altitude environment, and the main use of oxygen is to participateoxidative phosphorylation and to produce energy, therefore, the energy metabolism of skeletalmuscle and brain are extremely important for maintaining exercise in high altitude. Researchhad showed hypoxia doesn’t have any significantly impact on contraction properties andmaximal voluntary contraction (MVC), only decrease the endurance time when skeletalmuscle contract at a low MVC. Brain is the most sensitive organ to hypoxia, which consumesa great amount of oxygen and has a very high metabolic rate. Hypoxia can directly inhibit thecentral nervous system (CNS) and cause a reduced electroencephalographic (EEG) activity.On the other hand, hypoxia can also increase the firing frequency of Ⅲ/Ⅳ afferent fibers andsubsequently inhibit the CNS and α motor neurons. Therefore, we speculated that CNS mightplay a more important role in physical performance reduction caused by hypoxia whencompared with peripheral factors.To explore the peripheral and central mechanism that hypoxia-caused reduction inphysical performance, this research evaluated the peripheral fatigue of rats exercise at sealevel and at stimulated altitude by detecting the skeletal muscle pAMPK/AMPK, skeletal muscle glycogen, blood lactate, and evaluated the central fatigue of them by detectinglocomotion, DOPAC/DA,5-HIAA/5-HT.Method:Rats were submitted to a10mins adaptive swimming everyday for7days. Rats wererandomly divided into sea level group and high altitude group. The rats in sea level groupwere housed and exercise at normoxia; the rats in high altitude group were subjected to astimulated5000m high altitude in a hypobaric chamber for24h and exercise in the chamber.To eliminate the air dissolved in water, swimming water was boiled one day before theexperiment. Rats swam with a weight (2.5%of body weight) attached to the root of its’ tailand were killed before the exercise, exercise for30min and exercise to exhaustion in eachgroup. Muscle glycogen, blood lactate, pAMPK/AMPK, pERK, DA, DOPAC,5-HT,5-HIAAand locomotion were determined.Result:1. After24h hypoxia in a stimulated5000m altitude, high altitude group has asignificantly lower exhaustion time (37±9min) compared with sea level group (91±16min).Rats in high altitude group show a sign to exhaustion (sunk into the water repeatedly) whenswimming for30min, while rats in sea level group didn’t show any sign to exhaustion whenswimming for the same period.2. Altitude group has a significantly higher gastrocnemius glycogen (3.88±1.01mg/g)compared with the sea level group (2.32±0.67mg/g) at rest. Gastrocnemius glycogen of bothgroup decreased significantly after exercise. However, at the moment of exhaustion, highaltitude group still has a significantly gastrocnemius glycogen (1.60±0.38mg/g vs1.10±0.30mg/g).3. At rest, high altitude group has a significantly lower pAMPK/AMPK ratio comparedwith sea level group. After exercise, the ratio in both group increased significantly. However,at the moment of exhaustion, high altitude group still has a significantly lowerpAMPK/AMPK ratio.4. At rest, high altitude group has a slightly but significantly increase in blood lactateconcentration (1.50±0.29mmol/L vs1.20±0.21mmol/L). However, at exhaustion, high altitudegroup has a significantly lower blood lactate concentration compared with sea level group(9.93±2.10mmol/L vs10.46±2.20mmol/L). 5. After stopping exercise, sea level group had a better recovery in blood lactateconcentration, which is significantly lower at10mins after the exercise than at the exhaustion.Blood lactate concentration in high altitude group didn’t decrease in the first10mins stoppingexercise. Instead it reached the summit at10mins after the exercise and still has nosignificantly difference at60mins after the exercise when compared with at exhaustion.6. After recording the locomotion, high altitude group had a significantly lowerlocomotion in every5min except the first5min compared with the sea level group. And thetotal locomotion of high altitude group is also significantly lower than sea level group(2040±670cm vs4308±973cm).7. Hypoxia and exercise has no significantly impact on phosphorylation of AMPK inmotor cortex and striatum. And pAMPK immunohistochemical stain also showed there isn’tany difference in motor cortex and striatum in each group. Though there are a fewpAMPK-positive neurons in cornu anterius medullae spinalis, there isn’t any significantlydifference between each group.8. There are significantly less pERK-positive neurons in motor cortex of high altitudegroup than of sea level group. Exercise has no significantly impact on phosphorylation ofERK in both groups.9. Hypoxia significantly increased striatal and cortical serotonin (5-HT). At sea level,cortical and striatal serotonin significantly increased after exercise. However, at stimulatedaltitude, there isn’t any significantly change in cortical and striatal5-HT.10. Hypoxia didn’t change the DA turnover (DOPAC/DA) and5-HT turnover(5-HIAA/5-HT) at rest. After the exercise, the DA turnover decreased and5-HT turnoverincreased in striatum of high altitude group compared with sea level group.Conclusion:1. By boiling the water for swimming before experiment, the bubbles attached to rats’ furcan be totally eliminated when they swim in a hypobaric chamber, and we established a stablemodel for evaluating the physical performance of rats. Using this model, after exposing tostimulated5000m altitude for one day, rats swimming in hypobaric chamber had anexhaustion time of only40%of rats swimming in sea level.2. At the moment of exhaustion, high altitude group had a significantly lowerpAMPK/AMPK ratio and blood lactate concentration compared with sea level group, while the surplus gastrocnemius glycogen were significantly higher than sea level group, whichsuggested that the energy status of high altitude group were better than sea level group. Theseresults indicated that in the early time of exposing to high altitude, peripheral factor may notresponsible for reduced physical performance while CNS might play a more important role.3. After exposing to high altitude, the suppression of CNS, activated5-HT system anddepressed DA system in brain might be one of the mechanisms that induced the reduction ofphysical performance in high altitude.