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Preliminary Studies on Anti-hypoxia Effects of 1-Octacosanol

Author: HuiJin
Tutor: GaoWenXiang
School: Third Military Medical University
Course: Pathophysiology
Keywords: Octacosanol Anti-hypoxia Cardiac hypertrophy Pulmonary vascular remodeling Mitochondria
CLC: R285
Type: Master's thesis
Year: 2007
Downloads: 116
Quote: 4
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Abstract


Plains people into altitude hypoxia environment, the ability to work and work efficiency decline, some people may be due to poor acclimatization to altitude sickness occurs, serious and even life-threatening. Therefore, the search for effective pro-altitude hypoxia acclimatization measures to improve the quality of life and ability to work highland residents altitude hypoxia environment, promote their hypoxic acclimatization process, to reduce the incidence and mortality of altitude sickness, High Altitude Medicine The focus of the study, and cutting-edge. Drugs for high altitude acclimatization, prevention and treatment of altitude sickness is easy, feasibility, and related personnel has been committed to the anti-hypoxia drug to find. Acetazolamide, dexamethasone, theophylline and other drugs on the plateau hypoxia symptoms have some relief, but side effects limit its practical use. Medlar, ginkgo biloba, ginseng and other medicinal and edible raw materials as the main ingredient produced Antianoxia food additives can significantly prolonged hypoxia animal survival time, reduce the incidence of acute mountain sickness into the plateau forces, improve plateau ability to work, but resources less expensive, is not conducive to the promotion of use. Octacosanol (1-Octacosanol) is a naturally occurring fatty alcohol, widely distributed in the animal's skin and visceral, waxy secretion of the insect, and plant roots, stems, leaves, shells, kernel lipid wide range of sources, with no side effects, as a natural health food additives and a broad spectrum of natural medicine, has been used in the field of sports drinks, natural health products, pharmaceuticals and cosmetics. Studies have shown that Octacosanol with a variety of physiological functions, including anti-motility fatigue, enhance endurance, energy and stamina, lowering blood pressure, cardiovascular disease prevention, anti-platelet aggregation, cell protective effect on the heart and brain ischemia protective effect, suggesting Octacosanol may be an effective the Hypoxia Tolerance food, but about its anti-hypoxia effect so far domestic and outside have not been reported. Therefore, this study observed three Octacosanol anti-hypoxia effect, and to explore its mechanism of action: 1. To establish atmospheric airtight hypoxia, sodium nitrite poisoning, brain ischemia and hypoxia and myocardial ischemia oxygen the four kinds hypoxia animal models, observed Octacosanol the impact of different types of acute hypoxic mice survival time; 2. establish chronic decompression hypoxia 30 d rat model to detect arterial blood gas, blood, and left and right ventricular hemodynamic parameters, right ventricular mass index, observe the morphological changes of the heart and pulmonary vascular; established rat model of chronic hypoxia 30 d, six animal treadmill, observed on chronic lack Octacosanol oxygen exercise endurance in rats, the detection of cardiac and skeletal muscle mitochondrial respiratory function and ATP synthesis rate and ATP decomposition rate. The results showed that: 1. Give 10 mg.kg -1 and 50 mg.kg -1 Octacosanol gavage mice confined anoxic survival time was significantly higher than control group, the survival time increased by 21.11% and 26.46%, respectively, compared with the control group, the difference was very significant (P <0.01); 100 mg.kg -1 Octacosanol gavage mouse Asia sodium nitrate poisoning survival time compared with the control group no significant difference (P> 0.05); given 50 mg.kg -1 Octacosanol gavage mice were decapitated mouth movement duration isoproterenol and injection sealed anoxic survival time was significantly higher than that in the control group (P <0.05); given 5 mg.kg -1 Octacosanol the intragastric chronic hypoxia mouse arterial partial pressure of oxygen (PO 2 ), oxygen saturation (SO 2 ), lactate (Lac), red blood cell (RBC), hemoglobin (Hb) with the control group showed no significant difference (P> 0.05) was significantly higher than that in the control group (P <0.01), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin ( MCH), red cell distribution width standard deviation (RDW-SD), red cell distribution width coefficient of variation (RDW-CV) was significantly lower than the control group (P <0.01); given 5 mg.kg -1 Octacosanol gavage chronic hypoxia rat right ventricular mass index (RVWI) was significantly lower than the control group (P <0.05), right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), pulmonary vasoconstriction pressure (PASP), pulmonary artery diastolic pressure (PADP), mean pulmonary artery pressure (MPA) and right ventricular pressure rise (or fall) the maximum rate (± dp / dtmax) were significantly lower than the control group (P <0.05), the two groups of animals left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), aortic pressure (AP) and left ventricular pressure increase (or decrease) the maximum rate (± dp / dtmax) There was no significant difference (P> 0.05); gavage chronic the hypoxic rats sports exhaustive time. give 5 mg.kg in -1 Octacosanol significantly higher than those in the control group (P <0.01), the myocardial mitochondrial IV state breathing (ST < sub> 4 ) was significantly lower than the control group (P <0.01), respiratory control rate (RCR), phosphorus oxygen ratio (P / O), ATP synthesis rate was significantly higher than that in the control group (P <0.05), two group of animals myocardial mitochondrial III state breathing the ST 3 and oxidative phosphorylation efficiency (OPR), skeletal muscle mitochondria III state breathing (ST 3 ), mitochondrial IV state breathing (ST < sub> 4 ), respiratory control ratio (RCR) and oxidative phosphorylation efficiency (OPR) is not a significant difference (P> 0.05). Conclusion: 1. Octacosanol can be significantly enhanced hypoxic tolerance in mice to reduce brain energy consumption, improve myocardial hypoxia significantly prolong the survival time of mice in the atmospheric pressure in a confined environment; Twenty eight alkanol not improve the body's oxygen transport efficiency, but can improve a single red blood cell hemoglobin concentration, reduced red blood cell volume, helps reduce blood viscosity, improve microcirculation; 3. Octacosanol effective prevention and treatment of chronic hypoxia-induced pulmonary hypertension, relieve chronic hypoxia in rat pulmonary vascular remodeling and right ventricular hypertrophy inhibition in rats with chronic hypoxia, attenuate myocardial fibrosis; 4. Octacosanol can be significantly enhanced in rats with chronic hypoxia pole volume (aerobic) exercise capacity, and its mechanism may improve chronic hypoxia in rat heart mitochondrial oxidative respiration efficiency and ATP synthesis rate Octacosanol, improve chronic hypoxia in rat myocardial function.

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