Study On The Model Of Zebrafish Heart Injury Induced By Chemical Drugs And The Protective Effect Of Shengxian Decoction

Objective: The zebrafish heart injury model was induced by different chemical drugs and discussed.After the model was selected,the water extract of Shengxian Decoction was used to intervene to explore the protective effect of Shengxian Decoction on heart injury,and provide a certain treatment for the clinical treatment of cardiovascular disease,and provided a possible direction for the study of related mechanisms.Methods: Zebrafish(cmlc2-GFP)embryos with normal development after fertilization were selected and treated with aconitine,aristolochic acid,furazolidone and barium chloride.After the preparation of the model,the drug intervention was carried out by using the water extract of the Sheng Xian Decoction and the pharmacologically active ingredient of the drug,Astragaloside.Then observing the protective effect of Shengxian Decoction on heart injury by measuring the changes of heart rate,SV-BA spacing and cardiac morphology,and through the RNA-seq detection and network pharmacology analysis method for related indicators.Results:1.The zebrafish heart injury model induced by aconitine,aristolochic acid,furazolidone,barium chloride.(1)Aconitine 15mg/L can lead to increased heart rate of zebrafish,prolonged SV-BA spacing,pericardial edema and blood cell accumulation.(2)Aristolochic acid 5?mol can cause zebrafish heart rate to slow down,SV-BA spacing is prolonged,heart beat is weakened,etc.(3)Furazolidone16,32?g/ml can cause zebrafish heart rate to slow down,SV-BA spacing to prolong,blood cell accumulation.(4)barium chloride 0.05%,0.1% can cause zebrafish heart rate to slow down,SV-BA spacing is prolonged,and atrial ventricle is elongated.2.Through the drug screening experiment of Sheng Xian Decoction and Astragaloside,it was found that(1)Sheng Xian Decoction 20?g/ml and astragaloside 40?g/ml can antagonistic thearrhythmia caused by aconitine.(2)By RNA-seq detection of aconitine group,control group,aconitine plus Shengxian decoction group and aconitine plus astragaloside group,it was found that aconitine up-regulated the expression of SGK1,ATP2 A,NPY,CRHB,potassium channel related genes(KCNJ1A.3,KCNJ1 A.5,KCNJ1 A.6,KCNJ12B),and down-regulated the expression of SLC8A4 A,KCNB2,while Sheng Xian Decoction could decrease the expression of related genes such as NPY,CRHB,KCNA1 A,and up-regulated the expression of ATP1A1 A.2,at the same time it has a greater impact on glutamate synaptic pathways and GABAergic synaptic pathways.and astragaloside IV could increase the expression of SLC8A4 A,potassium channel related genes(KCNK5A,KCNA3 A,KCNA4,KCNA6A).(3)Network pharmacology analysis of the factors related to the treatment of arrhythmia in Shengxian Decoction,speculated that Shengxian Decoction may play a role in the treatment of arrhythmia by regulating sodium channel,potassium channel gene and affecting the expression of some genes in HIF-1 pathway,and the results are consistent partly with RNA-seq detection.Conclusion:1.Aconitine,aristolochic acid,furazolidone and strontium chloride can induce zebrafish heart damage,and the damage performance is different.2.Aconitine-induced zebrafish heart damage includes arrhythmia,which is related to aconitine-induced sodium channel,calcium channel,potassium channel dysregulation and sympathetic nerve excitation.3.Sheng Xian Decoction can antagonize aconitine induced arrhythmia,possibly by down-regulate the expression of NPY,CRHB related genes,and coordinate the balance of gabaergic synaptic and glutamatergic synapses,so inhibite sympathetic excitation,and astragaloside may play a role in antagonizing arrhythmia by regulating calcium channels.4.Sheng Xian Decoction treatment of arrhythmia may play a role by regulating the expression of sodium channel,potassium channel gene and influence the HIF-1pathway,which provides a certdirection for the clinical application of Sheng Xian Decoction in the treatment of arrhythmia-related diseases and related mechanisms research.