Preliminary Studies On Anti-hypoxia Effects Of 1-Octacosanol

It is well known that the physical working capacity and working performance are decreased when sea level residents ascent to the high altitude environment.Some people develop high altitude diseases because of poor acclimatization to hypoxia,or even lose their lives.For this reason,searches for methods of promoting acclimatization to high altitude environments,which will be able to improve life quality and working performance of high altitude residents,promote hypoxia acclimatization process,and reduce incidence and case fatality of high altitude diseases,arouses many researchers' concern in the field of high altitude medicine.Prophylaxis by drugs is a simple and convenient method to promote high altitude acclimatization and to prevent high altitude diseases.Previous researches suggested that western medicines such as acetazolamide,dexamethasone and theocin may ease off symptoms of high altitude hypoxia,nevertheless,the adverse reactions of those drugs limit the practical applications.Material which can be used as both food and drugs,such as barbary wolfberry fruit,ginkgo leaf and ginseng,could significantly prolong the survival time of hypoxic animals,reduce the incidence rate of acute high altitude sickness of plateau troops,as well as elevate the physical working capacity.However,because of their expensive price and less resource,the generalization is limited to some extent.1-Octacosanol is a purified fatty alcohol,which has been found in epidermis and internal organs of animals,wax secreted by insects,as well as root,stalk,leaf,shell and seed of plant.Because it is widely distributed and of no by-effects,it has become a natural healthy food additive and a broad-spectrum natural miracle drug as well,being utilized in fields of sport beverages,natural health products,medicine,cosmetics and so forth. Previous studies indicated that 1-octacosanol was of multiple physiological activities, including functions against exercise-induced fatigue,reinforcement of endurance capacity, vigour and physical strength,reduction of blood lipid,prevention of cardiovascular diseases, anti-platelet aggregation,cytoprotection and protection of ischemic heart and brain.Those above research results strongly indicate that 1-octacosanol may be a potential anti-hypoxia food,but anti-hypoxic effects of 1-octacosanol has not been reported so far.Accordingly, we observed in this study the anti-hypoxic effects of 1-octacosanol as follows,and the preliminary mechanisms were discussed:1.Four kinds of hypoxic animal models were set up and the survival time of acute hypoxic mice was observed;2.Thirty-day chronic hypoxic rat model was set up,and blood gas parameters,blood routine,haemodynamics parameters of right and left cardiac ventricle,right ventricle weight index,as well as morphological studies of pulmonary vessels and heart were analyzed;3.Thirty-day chronic hypoxia rat model was set up,the effect of 1-octacosanol on exercise tolerance was investigated,and the respiratory function of myocardial and skeletal muscle mitochondria,ATP synthesis and decompound rate were detected.The main results are summarized as follows:1.Mice administered 10mg.kg-1 and 50mg.kg^-1 1-octacosanol survived time significantly longer than the control when subjected to isobaric hypoxia(P＜0.01),while no difference were found between 100 mg.kg^-1 administration group and the control(P＞0.05). Persistence time of gape action after decapitation and tolerance time to isobaric hypoxia after isoprinosine administration were significantly longer(P＜0.05) in 50mg.kg^-1 1-octacosanol group than in the control group,respectively.2.Blood routine parameters,such as mean corpuscular hemoglobin concentration (MCHC),hematocrit(HCT),mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH),red cell distribution width standard deviation(RDW-SD) and red cell distribution width coefficient of variation(RDW-CV) were significantly lower in 5mg.kg^-1 1-octacosanol chronic hypoxia group than in the chronic hypoxia control group(P＜0.05). Arterial oxygen partial pressure and oxygen saturation,lactic acid,red blood cell count and hemoglobin concentration were not significantly different in these two groups(P＞0.05).3.Right ventricle weight index(RVWI),as well as right peak-value systolic pressure (RVSP),right value-end diastolic pressure(RVEDP),pulmonary arterial systolic pressure (PASP),pulmonary arterial diastolic pressure(PADP),pulmonary arterial mean blood pressure(PAP) and maximum increase and decline rate of right intraventricular pressure (±dp/dt_max),were lower in 5mg.kg^-1 1-octacosanol chronic hypoxia group than in the chronic hypoxia control group(P＜0.05).No significant difference was found in left peak-value systolic pressure(LVSP),left value-end diastolic pressure(LVEDP),aortic pressure and maximum increase and decline rate of left intraventricular pressure between these two groups.4.Exhaustive exercise time and myocardial mitochondrial respiratory state 4(ST₄) were significantly lower,while myocardial mitochondrial respiratory control rate(RCR), ADP/O ratio and ATP synthesis rate were significantly higher in 5mg.kg^-1 1-octacosanol chronic hypoxia group than in the chronic hypoxia control group(P＜0.05).There was no significant difference of myocardial mitochondrial respiratory state 3(ST₃) and oxidative phosphorylation ratio(OPR),as well as skeletal muscle mitochondrial ST₃,ST₄,RCR and OPR between these two groups(P＞0.05).The main conclusions are summarized as follows:1.1-Octacosanol can enhance hypoxia tolerance of mice,decrease cerebral energy consumption and relieve myocardial hypoxia injury;2.1-Octacosanol does not improve oxygen transport efficiency of organism, nevertheless,it can raise the haematoglobin density in single red blood cell and diminish the red blood volume,which helps to decrease blood viscosity and improve microcirculation;3.1-Octacosanol can effectively prevent pulmonary hypertension induced by chronic hypoxia,extenuate pulmonary vascular structural remodeling and myocardial fibrosis and thus inhibit right ventricular hypertrophy of chronic hypoxic rats;4.1-Octacosanol can significantly improve maximum exercise capacity of chronic hypoxic rats,of which,the mechanisms may be related with the elevation of oxidative phosphorylation efficiency and ATP synthesis rate of myocardial mitochondria so as to improve myocardial function of rats exposed to chronic hypoxia.