[Animal modeling] - Changes and significance of monocarboxylic acid transporters in cortex of rats with exercise fatigue under simulated plateau hypoxia environment

  Objective To investigate the relationship between the adaptation of exercise fatigue and the lactate transport and metabolism in cerebral cortex at high altitude.

  Methods Sixty three SD rats of clean grade were randomly divided into control group, routine exercise group, high altitude group, high altitude acclimatization 3 days group, high altitude acclimatization 1 week group, high altitude acclimatization 2 weeks group and lactate transporter inhibitor group (referred to as high altitude inhibitor group). In addition to the control group, the rats in each group established the treadmill exercise fatigue model under normal pressure and oxygen or simulated plateau low pressure and hypoxia respectively. The average exhaustion time was used to determine the change trend of exercise fatigue in rats. The expressions of monocarboxylate transporters 2 (MCT2) and MCT4 in motor cortex were detected by Western blot and immunohistochemistry. The pathological changes of delayed neurons in cerebral cortex were evaluated by Nissl staining, and the content of lactic acid in rat brain was determined.

  Results The average exhaustion time of rats in the high altitude group and the high altitude inhibitor group were (61.00 ± 6.55) min and (71.25 ± 9.59) min, respectively, which were significantly lower than those in the routine exercise group [(124.75 ± 9.36) min] and the high altitude acclimatization group [(100.25 ± 9.74) min, P<0.05]. Western blot analysis showed that the expression level of MCT2 in the cortex of brain motor area of rats in the two week high altitude acclimatization group and the high altitude inhibitor group was significantly higher than that in the control group, which was 120.6% and 164.4% respectively (P<0.05); The expression of MCT4 was 174.6% and 168.8% respectively (P<0.05). The results of immunoblotting were confirmed by immunohistochemistry. Under simulated high altitude environment, the average content of lactic acid in the brain of rats in each group was significantly higher than that in the normal exercise group [(0.175 ± 0.021) mmoL/g] (P<0.05). The pathological evaluation showed that the average neuron density (the number of neurons in each high power field) of the cerebral cortex in the high altitude group and the high altitude inhibitor group were 46.75 ± 8.65 and 63.50 ± 7.65, respectively, which were significantly lower than those in the control group (135.88 ± 8.59) (P<0.05); there="" was="" no="" significant="" difference="" between="" the="" two="" groups="" 121.75="" after="" acclimatization="" at="" high="" altitude="" for="" weeks="" p="">0.05).

  Conclusion The adaptability of the body to exercise fatigue after acclimatization at high altitude is related to the changes in the expression of MCT2 and MCT4 in the brain, which can be used as a target for medical intervention on exercise fatigue.