Study On The Anti-hypoxia Pharmacological Effects And Its Mechanism Of Ethanol Extract From Saussurea Involucrate Kar Et Kir

The thesis aimed to screen the anti-hypoxia active fraction from S. involucrata, and investigate the pharmacological mechanism of anti-hypoxia from the points of view of free radical metabolism, substance metabolism and energy metabolism.1. The survival time of hypoxia and plasma lactic acid in hypoxic mice under the normobaric hypoxia were used to compare the anti-hypoxic activity of each extraction of S. involucrata. The 70% ethanol extract of S. involucrata (EES) exhibited the best anti-hypoxia activity. Then, the normobaric hypoxia test, acute decompression model and chemical poisoning hypoxia model were used to study the anti-hypoxic effect of S. involucrata.2. 60 Male BABL/C mice were randomly divided into 6 groups of 10 animals of each group, namely normal control group, hypoxia model group (HYM), reference drug group, and 3 treatment group. The EES were intragastric administered to the mice by i.g. at the dosage of 250 mg·kg^-1, 500 mg·kg^-1 and 750 mg·kg ^-1. At the same time, normal control and hypoxia model group were treated with distilled water as a similar manner, respectively, The pharmacological mechanism of EES were studied through determination of the free radical metabolism, subtance metabolism and energy metabolism, and the selected indicators including: SOD activity and MDA content in hypoxic mouse plasma, brain and myocardial; water content of brain, heart and lung; blood glucose, liver glycogen, muscle glycogen, TG, TCH and HDL-C levels; protein content of cardiac and brain tissue; LDH activity and LD content of plasma, brain and heart; ATP content and ATPase activity of brain and heart tissue. Results: 1.The S. involucrata has good anti-hypoxia effect, 70 % ethanol extraction of S. involucrata was determined to be the best anti-hypoxia active fractions.2. Compared with the HYM, EES could significantly prolong the survival time of hypoxic mice. EES, at the doses of 250 mg·kg^-1 , 500 mg·kg^-1 and 750 mg·kg ^-1, significantly prolonged the survival time of mice under different hypoxic conditions with a dose dependent manner.3. Compared with the HYM, EES significantly increased SOD activity and decreased the MDA content in the plasma and tissue and reducing the free radical damage under hypoxic conditions.4. Compared with the HYM, EES significantly reduced the water content and organ index in brain, heart and lung of hypoxic mice; improved the level of glucose metabolism in the body; effectively reduced the TG, TCH levels and increased the HDL-C levels; improved the protein content of myocardial and brain tissue, indicating that EES effectively improved the substance metabolism level of the anoxic mice.5. Compared with the HYM, EES could increase LDH activity and lower LD levels in plasma and tissue of hypoxic mice, indicating that EES improved the body's anaerobic glycolysis and reducing acidosis. At the same time, EES increased the ATP content and ATP activity in hypoxic mice, indicating that EES improved the process of oxidation-phosphorylation electron transport and increased the energy conversion process of hypoxic mice.