Study Of The Mechanism By Which Rhodiola Rosea Extract Improves The Tolerance Of High-altitude Hypoxia In Mice

In recent years,more and more people who work and travel have entered high-altitude areas,but most people who enter the plateau quickly will be unable to adapt to the hypoxic environment of the plateau,which will induce oxidative stress in the body and damage the heart,lungs,and brain.In severe cases,it will lead to a series of diseases such as pulmonary edema and cerebral edema.Rhodiola rosea was one of the traditional "medicine and food homologous" Chinese medicinal materials.Studies had shown that its active ingredients could prevent and alleviate hypoxia damage in the body.Therefore,in this study,R.crenulata aqueous extract RCAE was used as the research object to construct a 6000 m(11.4% O2)plateau hypoxia mouse model.Mortality,apoptosis-related proteins,Ras/Raf/Erk/Mek/Hif-1α signaling pathway to explore the effect of RCAE on hypoxia tolerance in mice and the hypoxia protection effect on lung tissue,which was the basis for RCAE in anti-hypoxic organisms.Provide more scientific basis for the clinical application of protection.The main findings are as follows:1、Hypoxia can reduce the levels of GSH/GSSG and SOD in the serum,heart,lung and brain tissues of mice,and increase the content of LDH and MDA.This change was significantly mitigated in the low,medium to high dose group of RCAE,and the medium dose group was the most effective.Different RCAE pre-administration time groups can increase GSH/GSSG and SOD levels,reduce LDH and MDA content,and in general,the gastric filling time of RCAE-10 group is short and the effect is better.With the increase of altitude,the oxygen concentration gradually decreases,the GSH/GSSG and SOD levels gradually decrease,and the LDH and MDA content gradually increases.RCAE can adjust the level of oxidative stress in mouse serum and lung tissue at an altitude oxygen concentration of 6000 m,and the difference in the hypoxia 3000 m group is not significant.2、 The lung tissue of hypoxic mice showed a variety of pathological damage such as structural disorders,thickening of alveolar walls,destruction of reticular structures,loss of normal alveoli,and a large number of inflammatory cell infiltration.RCAE significantly reduces these pathological changes.The lung tissue of the mice in the RCAE-H group was structurally intact,there was a small amount of inflammatory cell infiltration,and there was no significant thickening of the alveolar wall.Apoptosis rate of TUNEL-positive cells in hypoxic mice with alveolar septum was42.23%.The low,medium and high dose groups could reduce the apoptosis rate and showed a dose dependence,and the high dose group had the lowest apoptosis rate.Hypoxic mice had disordered myocardial fiber structure,increased spacing,uneven cytoplasm coloration,and inflammatory infiltration of tissues.RCAE treatment can improve the myocardial fiber disorder in mice,so that the cardiomyocyte morphology is normal and the structure is more complete.The cell structure in the hippocampal tissue of hypoxic mice is destroyed,the neuronal loss is serious,the nerve cells are atrophied,the nuclei are solidified into triangles or polygons,the cell morphology is seriously deformed,the nucleoli disappears,and there are few normal cells.RCAE alleviated the damage of hypoxia to neurons,and the damage to cells and neuronal cells was significantly reduced,the number of cells increased,the abnormal neuronal structure was reduced,and the phenomenon of nuclear consolidation was significantly reduced.And with the gradual increase of the dose,the therapeutic effect gradually increased,and the high dose group was the best.3 、 Hypoxia upregulated the expression of pro-apoptotic proteins Bax and Caspase 3 in mouse lung tissues(p<0.05),and the expression of anti-apoptotic protein Bcl-2m RNA(p<0.05),and significantly reduced the ratio of Bcl-2/Bax(p<0.05).The protein expression results were consistent with the m RNA expression results of1.57-fold,1.44-fold,0.78-fold and 0.49-fold of the NC group,respectively.RCAE reduced the m RNA and protein expression(p<0.05)of Casparse 3 and Bax,and increased the ratio of m RNA,protein expression(p<0.05)and Bcl-2/Bax of Bcl-2.The m RNA expression of Ras,Raf,Erk,Mek,hif-1α in the lung tissues of hypoxic mice was significantly upregulated(p<0.05),which was 1.79-fold,2.04-fold,1.27-fold,1.88-fold,and 2.94-fold in the NC group,respectively.Hypoxia activates the Ras/Raf/Erk/Mek signaling pathway,and RCAE inhibits the expression of these genes and downregulates the expression of Hif-1α m RNA.Conclusion: The higher the altitude and the lower the oxygen concentration,the stronger the oxidative stress of the mouse body and the more serious the degree of lipid peroxidation.RCAE can improve the hypoxia tolerance of mice and reduce the level of oxidative stress in the heart,lungs and brain tissue caused by hypoxia,the optimal dose is medium dose(2 g/kg),the optimal pre-administration time is 10 d,and the oxidative stress level at 6000 m can be reduced to 3000 m.RCAE can improve the tolerance of hypoxia in mice to alleviate pathological damage to the heart,lungs and brain tissue of mice caused by hypoxia.RCAE may reduce apoptosis due to hypoxia by increasing anti-apoptotic proteins,reducing pro-apoptotic protein expression to reduce apoptosis due to hypoxia,and improving hypoxia tolerance in mice by inhibiting the Ras/Raf/Erk/Mek/Hif-1α signaling pathway,alleviating hypoxia-induced lung damage.