The Anti-hypoxia Effect Of Saussurea Involucrate Capsule And Its Mechanism

Objective:To build an animal model to investigate the demage after mice were exposed to hypoxia environment (8000m) by decompression chamber and to estimate the protective effects of Saussurea involucrate capsule on brain and heart of hypoxic mice and its mechanism.Method:1.The rats were exposed continuously to a simulated high altitude of8000m for6h、9h、12h、24h、48h and72h in an animal decompression chamber. Assess the Morphological changes (transmission electron microscopy by HE Stain and transmission electron microscopy). changes of LD contend LDH activity ATPase activity and T-AOC ability and mRNA expression of HIF-1α、VEGF、Caspase-3.Select an applicable time tor anti-hypocia drug evaluation.2.The BALB/c mouse models of normbaric hypoxia and decompression hypoxia were used to evaluate the survival time of mice in hypoxia after given different doses of the Saussurea involuerate capsule.The most effective does was settled.3..Randomly divided the BALB/c mouse into normal group (N)、hypoxic model groupe (M)> acetazolamide group (ACZ) and Saussurea involucrate capsule group (XLJN). Drugs were administered orally and the mice were exposed continuously to a simulated high altitude of8000m for9hours in an animal decompression chamber. Both the morphological changes and the oxidative stress markers were estimated to evaluate the protective effect of the flavone capsule. Test the mRNA expression of HIF-la、VEGF、SOD and CAT by RT-PCR and the content of protein by Western-blot to investigate the mechanism of the protective effect of Saussurea involucrate capsule.4. Use Morris water maze to assessing spatial related forms of learning and memory.5days of Spatial learning experiment and the following probe trial are settled.Result:1. Both the morphological changes and the changes of LD、LDH、T-AOC、ATPase in brain and heart were abserved in each model with the extended hypoxic period. Morphological demage appeared,LD contant increased and the T-AOC ability decreased after6h;the activity of LDH increased and ATPase decreased after12h’s exposion.2. Compared to the model group, at the dosage of all three dose enhanced the survival time of mice in both normbaric and decompression hypoxia models. The most effective dose is500mg/Kg.3. The Saussurea involucrate capsule palliate the damage of neurons after exposed to the hypoxic environment, indicating that flavone capsule protect the structure of neurons and mitochondrias.The capsule could also increase Ca2+-Mg2+-ATPase、PK、T-AOC activities, and decrease the content of LD、 MDA、MPO in brain. At the same time,mRNA and protein expression of HIF-1α、VEGF decreased and SOD、CAT increasd in the XLJN group.4.Both escape latency and path length were decreased after training for the mice to find the hided platform. The detailed analysis revealed that the mice in model (M) group took significantly more time in comparison with normal(N) group. There were no statistically significant difference between the N group and XLJN group...