Preliminary Study On The Protective Effect Of Adiantum Capillus-veneris L. Extraction On CMS Rats

Objective:The model in which rats with chronic mountain sickness(CMS)were established,the intervention of the extraction of Adiantum capillus-veneris L.were investigated by pulmonary artery pressure,serology and pathology and the effect of the Adiantum capillus-veneris L.extraction on serum metabolic markers in rats with CMS was further analyzed by ~1H-NMR at the level of metabolomics.Methods:To divided 50SD rats into different groups namely control group(CG),model group(MG),nifedipine positive control group(NE),alcohol group of Adiantum capillus-veneris L.(ACVL.AG)and water group of Adiantum capillus-veneris L.(ACVL.WG),which means 10 rats in each group.Among them rats in CG were fed for 45 days under plain conditions without any intervention.The remaining four groups were fed in the simulating high altitude environment for 30 days in order to give 15 days of intervention after completion of the modeling.1)Whether the CMS model of the rats in the artificial laboratory chamber with simulated altitude above 5000 m were successfully established based on the level of pulmonary artery pressure in rats of each group.Subsequently,serum C-reactive protein(CRP),apolipoprotein-A1(Apo-A1),erythropoietin(EPO)and vascular endothelial growth factor(VEGF)were measured.The protective effect of Adiantum capillus-veneris L.extraction on rats with CMS were evaluated by observing the two indexes.2)To evaluate the intervention effect of Adiantum capillus-veneris L.on rats with CMS and to confirm establishment of CMS model,the pulmonary artery tissues of each group were taken out to make frozen sections,and the morphological structure of pulmonary artery tissues were observed.To further explore the anti-inflammatory effect of Adiantum capillus-veneris L.extraction,the heart,lung and brain tissues of each group were also taken out to make pathological sections and morphological structure were observed by light microscopy.3)To divided 40 SD rats into different groups namely control group(CG),model group(MG),nifedipine positive control group(NE),alcohol group of Adiantum capillus-veneris L.(ACVLAG)and water group of Adiantum capillus-veneris L.(ACVL.WG),which means 8 rats in each group.Among them rats in CG were fed for45 days under plain conditions without any intervention.The remaining four groups were fed in the simulating high altitude environment for 30 days in order to give 15 days of intervention after completion of the modeling.~1H-NMR method of metabolomics were used to establish the serum metabolic fingerprints of rats in each group.Partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used for statistical analysis to clarify the differential metabolites in serum of rats in each group.Results:1)The pulmonary artery pressure of rats with CMS were significantly increased,which indicated that the CMS model were established successfully.The positive drug and the extraction of Adiantum capillus-veneris L.could decrease the pulmonary artery pressure of rats with CMS(P<0.05).The extraction of Adiantum capillus-veneris L.could down-regulate the levels of CRP,EPO and VEGF and up-regulate the level of Apo-A1(P<0.05),suggesting that the extraction of Adiantum capillus-veneris L.have protective effects on rats with CMS.2)Light microscopy showed that the pulmonary artery,heart,lung and brain tissues of rats with CMS were damaged to varying degrees.The extraction of Adiantum capillus-veneris L.could alleviate the damage of pulmonary artery,heart,lung and brain tissues of rats with CMS,which may be related to the anti-inflammatory effect of Adiantum capillus-veneris L.extraction.3)The serum metabolites were determined by ~1H-NMR method.It was found that CMS resulted in changes of 16 metabolic markers in rats serum.Compared with CG,the levels of leucine,valine,threonine,methionine,pyruvic acid,glutamic acid,tyrosine,creatine and lactic acid increased and the inositol decreased in MG(P<0.05).The levels of leucine,creatine,methionine,pyruvate,glutamic acid and creatine in rats with CMS were decreased by the extraction of Adiantum capillus-veneris L.(P<0.05).The results showed that the extraction of Adiantum capillus-veneris L.could improve the metabolism of rats with CMS.Conclusion:The extraction of Adiantum capillus-veneris L.have protective effects on rats with CMS and the effects of ethanol extract of Adiantum capillus-veneris L.were most obvious,and its mechanism may be related to its anti-inflammatory,anti-hypoxia effect and promotion of multiple metabolic pathways in rats with CMS.