Study On Physiological And Biochemical Mechanisms Of Hypoxia Adaptation In Three Small Mammals

Pamirs to the west,Hengduan Mountains to the east,Kunlun Mountains and Qilian Mountains to the north,Himalayan to the south and with an average elevation exceeding 4,500 metres,the Tibetan Plateau is sometimes called "the Roof of the World",being the world's highest and largest plateau with an area of 2,500,000 square kilometres,and sometimes termed the Third Pole.Different biologies living in the Tibetan Plateau has formed their unique adaptation mechanisms to adapt the extreme natural conditions such as thin air,cold and dry,strong ultraviolet radiation and so on.Oxygen is the limiting factor for the survival of animals,it plays a vital role in their growth,development and physiological activities.As a stressor,Hypoxia can cause a series of stress responses,such as metabolic disturbance,tissue damage,increase of oxygen free radicals,destruction of nucleic acid structure,damage of cell membrane,and even lead to death of animals.Plateau Indigenous organism has formed a unique physiological mechanism for the low oxygen environment in the long evolutionary process.The existence of a number of stable mechanism such as Cardiovascular system,respiratory system and neuroendocrine system and so on,makes the body can compensate for the oxygen level of the stable tissue under hypoxia stress.After long-term natural selection,These species obtain the hereditary structure,function and features of habits,which makes them can thrive in plateau environment.The organ level,the cellular and subcellular level about oxygen uptake and utilization,the expression regulation of hypoxia related genes at the molecular level,multiple systems involving respiratory,cardiovascular,endocrine and so on,and metabolism reflected these adaptations.In this paper,three kinds of small native Tibetan mammals,Plateau Pika?Oehorona curzoniae?,Root Vole?Microtus oeconomus?and Gansu Zokor?Myospalax cansus?,are chose as the research object.Under the hypoxia environment,the cardiovascular system,respiratory system,musculoskeletal system and the dynamic change of functional gene level of the 3 kinds of small native Tibetan mammals are anaiysed to clear the physiological and biochemical adaptation mechanism,to analysis the function of each system,to compare the hypoxic adaptation ability of this 3 kinds of animals,to explore the differences and relations of hypoxia adaptation and adaptation mechanism between different species,and to further develop environmental stress and genetic evolutionary biology theory.The main conclusions are as follows:1.During the adaptation process to hypoxia,the Red blood cell count?RBC?,the hemoglobin concentration?Hb? and the Hematocrit?HCT? of 3 kinds of small mammals shows an increasing trend,but the mean red cell volume?MCV? and the mean red cell hemoglobin concentration?MCHC? declines.Under the low oxygen environment of simulated altitude 5000 m and 8000 m,the Hbv?Hctv?P_aco2?P_vco2 of 3 kinds of mammals changes significantly?P<0.05?,while there are no significant differences among the other indicators?P>0.05?.2.The Red blood cell count,the hemoglobin concentration and the Hematocrit of the 3 kinds of animals presents an upward trend with increased exposure time under low oxygen environment.In addition,blood pH and carbon dioxide partial pressure decreased.The oxygen saturation of Plateau Pika and Gansu Zokor performed a rising curve,but this indicator of Root Vole reduced.P₅₀ of Plateau Pika and Gansu Zokor in each group was in the maximum 2300 m,minimum 8000 m-25 d.This indicates that their oxygenation capacity is the smallest at the 2300 m and the largest at the 8000 m-25 d.From large to small,the order of P50 of Root Vole is 5000 m-25 d>8000 m-7 d>8000 m-14 d>5000 m-7 d>2300 m.This indicates that it's oxygenation capacity is the largest at the 2300 m and the smallest at the 5000 m-25 d.3.With the elevation of simulated altitude,the weight gain trend of right ventricle was more significant than that of the left for Plateau Pika and Gansu Zokor.In the process of hypoxia stress no matter 5000 meters or 8000 meters,HW/BW,RVW/BW,LVW/BW and RVW/LVW of these 2 kinds of animals showed a rising trend and the weight gain trend of right ventricle was more significant than that of the left?P<0.05?since the fourteenth day.This suggests that cardiac enlargement is mainly due to the thickening of the left ventricular wall in the process of hypoxia adaptation of these two kinds of animals.At the same time,it also suggested that the cardiac output per stroke of the hypoxia adaptation high altitude animals increased and that the ability of pumping blood was strengthened to improve oxygen supply capacity of whole body tissue.HW/BW,RVW/BW,LVW/BW and RVW/LVW of Root Vole are all higher than that of Plateau Pika and Gansu Zokor.And with the same time length of hypoxic adaptation,various indicators of 8000 meters above sea level are higher than the corresponding indicators of 5000 meters.The results showed that with the increase of altitude,various organs of the body will start the corresponding hypoxia emergency response mechanism to a greater extent.4.Along with the enhancement of hypoxia stress,LDH of Plateau Pika and Gansu Zokor showed an upward trend but no significant difference?P>0.05?.During this process,the T_co2 of the 3 animals showed a decreasing trend.And in the same situation,T_co2 of Plateau Pika and Gansu Zokor are higher than that of Root Vole?P<0.05?.5.Under hypoxia stress,the level of HIF-1? of Plateau Pika and Gansu Zokor during oxidation and glycolysis in muscle is lower than that of Root Vole in the comparison between different species,and the level of HIF-1? of Plateau Pika,Gansu Zokor and Root Vole are significantly higher than that of normal oxygen control group but no significant difference between groups in the comparison between different treatment groups of the same species?P>0.05?.In oxidative muscle tissue,the Percentage increase of HIF-1? of Root Vole is 79±5%,and that of Plateau Pika is 49±4%,and that of Gansu Zokor is 58±4%.In the muscle tissue of the fermentation of sugar,the Percentage increase of HIF-1? of Root Vole is 98±6%,and that of Plateau Pika is 65±5%,and that of Gansu Zokor is 73±4%.Under the condition of hypoxia stress,there is a linear relationship between the increase of HIF-1? and VEGF in oxidative muscle and that in glycolysis muscle of skeletal muscle of 3 kinds of animals.6.Under normal oxygen condition,there was no significant difference in cardiac enzyme activity of 3 kinds of animals?P>0.05?.Under hypoxia stress,three animals showed different changes in cardiac enzyme activity,that the increase of SOD activity,CAT activity and GR activity of Plateau Pika and Gansu Zokor were significantly higher than that of Root Voles.7.After the hypoxia stress,three kinds of small mammals showed a large difference in the change of the activity of ATP,that Ca²⁺-ATP enzymatic activity and Na⁺ K⁺-ATP enzymatic activity are significantly higher than that of Root Voles?P<0.05?.This can make sure that intracellular ion concentration is maintained at a relatively stable level.The tendency of a slight decline emerging later may be due to that the body of Plateau Pika and Gansu Zokor has produced adaptability in the process of adapting to the hypoxic environment and that the intracellular environment has been stable.