Comparative Research On Physiological Adaptations To Hypoxic Stress Between Mandarin Vole And Kunming Mouse

Mandarin vole(Lasiopodomys mandarinus), occurred plain region with lower altitude, spends almost all its life span underground. It is inevitably evolved adaption to normbaric hypoxia conditions underground. To understand the mechanisms behind these adaptations, to provide basic data for evolutionary biology of Mandarin vole, and to get clue for studying the mechanism of hypoxic disease and treating methodsin human, by employing female Kunming mouse (Mus musculus) as control, we studied the response of Mandarin vole to acute normbaric hypoxia (15.0%,10.0%,5.0% O2, 4 hr) and chronic normbaric hypoxia (10.0% O2,4 hr/d,4w), respectively. The expressions of HIF-1α, EPO, VEGF and CRH in kidney were tested by ELISA; the expressions of sex hormone in feces were tested; the changes of lung air-blood barrier were measured by electron microscope; the hemogram and capillary density in cardiac muscle were measured. Our research focused on HIF-la-EPO-hemogram, HIF-la-VEGF-capillary density, HPA and HPG axis, and lung status under chronic hypoxia. The results from this research are as follows:1) HIF-1α-EPO-hemogram:Under acute hypoxia, the expression of HIF-1αin mandarin voles increased, especially significant at 5.0% oxygen level, while no obvious changes in Kunming mouse was found. The expressions of EPO in both two rodents were decreased with decreasing of oxygen concentration except the 5.0%, but mandarin vole achieved significant just at 15.0%. The indices including hemogram, RBC and HGB changed insignificantly in both two rodents, whereas MCV decreased gradually following the oxygen tense, and Kunming mouse appeared to varied more abruptly. Under chronic hypoxic treatment, HIF-la increased in both rodents, the amount in Mandarin vole was 1.55 times than Kunming mouse. No significant differences existed between two rodents. The HCT, HGB and MCH were all significantly increased in two rodents and more abruptly change was detected in Kunming mouse.2) HIF-la-VEGF-capillary density:Under acute hypoxia, expression of VEGF changed insignificantly following oxygen tense in both Mandarin vole and KM mouse, so did the capillary density. However, under chronic hypoxia, expression of VEGF increased 1.4 times in Mandarin vole than that in KM mouse, but the capillary density in Mandarin vole didn't change, unlike in KM mouse that showed a great increase. The capillary density in Mandarin vole was significantly higher than that in KM mouse before and after hypoxic treatment.3) HPA and HPG axis:Under acute hypoxia, the ovary in Mandarin vole and uterus in KM mouse increased following the oxygen stress, except for the CRH expression. What's more, the expression of cortisol increased seriously in Mandarin vole, but not in KM mouse, there were a great decrease in the expression of estradiol. Under chronic hypoxia, the expression of VEGF increased both in Mandarin vole and KM mouse, and Mandarin vole presented a significant level. The expression of cortisol increased in Mandarin vole, while decreased in KM mouse after the chronic hypoxic treatment.4) Lung:The weight of Lung in Mandarin vole was much lighter and the gas-blood barrier significantly thinner than that in KM mouse. However, the the gas-blood barrier didn't change in Mandarin vole, while significantly decreased in KM mouse after chronic hypoxic treatment.In summary, the results from this research indicate that:1) Mandarin vole and KM mouse both increased the expression of HIF-la to regulate EPO expression for controlling the hemogram both under acute and chronic hypoxia. They responses to the acute hypoxia mainly decrease the resistance in blood circulation, and increase oxygen transport speed by decreasing the MCV. However, when responding to chronic hypoxia, they were mainly increase oxygen carry by increasing HCT and MCH. The KM mouse reflected more abruptly on hemogram.2) Mandarin vole and KM mouse didn't show any change in VEGF expression and capillary density, and this seems not key approach in responding to acute hypoxia. Under chronic hypoxic treatment, however, the expression of VEGF greatly increased in both rodents to regulate the capillary density, and it significantly increased in KM mouse.3) The acute hypoxia ttrigger the HPA and HPG axis to regulate metabolism and control the energy consumption. But after chronic hypoxic treatment, they all adapted and didn't show any change.4) Under chronic hypoxia treatment, the gas-blood barrier was thinner and changed insignificantly in Mandarin vole, howerver it became thinner in KM mouse.5) At normal condition, the Mandarin vole posses significantly lower HIF-la expression, higher capillary density and thinner lung gas blood barrier than those in KM mouse. There were more RBC, smaller MCV, higher MCHC, less MBC and PLT in Mandarin vole than those in KM mouse. The above adaptations indicated that subterranean Mandarin vole can effectively respond hypoxia conditions.