Cardiotoxicity Study Of Asarum In SD Rats On Pharmacology And NMR Metabolomics

PurposeTo probe the effect of pathological long-term toxicity of Asarum cardiotoxicity on SD rats with NMR techniques combined with conventional biochemical and pathological means.Methods60 screened from 80 SD rats are randomly divided into four experimental groups: control group, low dose group,middle dose group and high dose group of Asarum. Each group is 15.All rats are gavaged once a day, which last 28 days.On the 0th,14^th and 28^th day after administrated,the electrocardiogram is texted. Routine blood,blood biochemical and electron microscopy analysis are measured,and collecting serum and myocardial tissue is to determine their ¹H nuclear magnetic spectra and on the 28^th of the experiment ends. Result1.Electrocardiogram: Compared with the previous self-administration and the control group over the same period, there is no changes in electrocardiogram of the rat in low dose group.In the middle dose group, the heart rate decreases after the 28^th gavage?P<0.05 or P<0.01?. In the high group,the heart rate begins to slow down after the 14^th gavage?P<0.05?,but on the 28 th,the heart rate continues to decrease?P<0.01?.2. Myocardial enzymes:Compared with the control group,in low dose group,the content of myocardial enzymes of the rats serum has no change significantly?P>0.05?,but which increase obviously in the middle dose group?P<0.05 or P<0.01?, and in the high dose group,only the content of LDH increase significantly?P<0.01?. Compared with the middle dose group, in the high dose group, the content of CK, CK-MB and LDH levels decrease?P<0.05 or P<0.01?.3.Myocardial electron microscopy structure:in the blank control group, the mitochondria are dense,of which cristae arrange orderly and matrix are thick in myocardial cells;in the low dose group,the mitochondria show little swelling and cristae arranged disorderly slightly in cardiomyocytes;in the middle dose group,more the mitochondria apprare to swell and arrange disorderly,and even individual mitochondria show vacuoles degeneration and concentric degeneration;in the high dose group,the mitochondria showe significant degeneration, necrosis, and crest membrane damaged with hollow shape.4.¹H NMR metabolism: NMR spectrum of the serum and myocardial tissues change significantly,in which there are more than 20 biomarkers detected respectively. The result of PCA and PLS-DA show that each dose group and control focus respectively on the scatter distribution,and the greater the dose, the farther away from the control group.Compared with the control group, the variability of metabolin of serum in each dose group are that in the high dose group,the content of lipids,lactate,alanine,pyruvate, dimethylglycine ?-Glucose,?-glucose increase,and the content of glutamate, tyrosine decrease; in the middle dose group,the content of lactate pyruvate, dimethylglycine increase,and the content of glutamate, ?-Glucose,?-glucose decrease; in the low dose group,the content of ?-Glucose,?-glucose decrease.The variability of metabolin of myocardial tissu in each dose group are that in the high dose group,the content of lactate, malic acid, creatine, choline, ?-Glucose,?-glucose, fumarat,hypoxanthine increase,and the content of isoleucine, alanine,glutamine,arginine,taurine,tyrosine,xanthine decrease;in the middle dose group,the content of lactate, hypoxanthine increase,and the content of isoleucine, alanine,glutamine,creatine,arginine,taurine,?-glucose,?-glucose,tyrosine and xanthine decrease;in the low dose group,the content of creatine, ?-glucose, ?-glucose decrease. Conclusion1.The asarum on heart function and structure caused some damage, mitochondrial damage may be the one of the main targets. Asarum on heart toxicity and its drug dosage has very close connection, namely, the low dose of asarum, the extent of damage to light; On the other hand, the degree of damage.2. The role of cardiac toxicity of Asarum mechanisms is in relationship with energy metabolism, lipid metabolism, glucose metabolism, amino acid metabolism and purine nucleotide related metabolic disorders.