Study On The Mechanism Of Action Of Yixin Fumai Granules In Treating Sick Sinus Syndrome Based On Network Pharmacolog

Objective: To study the effect of Yixin-Fumai granules on the sinoatrial node function and on preventing tissue damage and the progress of Sinus atrial node of Sick Sinus Syndrome model in Mice with Sinus Node Fibrosis.Then using network pharmacology research to analyze the effect of Yixin-Fumai granules to the molecular targets and mechanism to Sick sinus Symdrome.Methods: The micro osmotic pump was surgically implanted into the neck and back of mice of Sick Sinus Syndrome model group(SSS group)and Yixin-Fumai granules treatment group(YXFM group)for subcutaneous pumping into Ang II,and the SAN fibrosis model mice were created,resulting in pathological injury reaction of SA fibrosis.The control group underwent surgery in the same way without pumping Ang II.SSS group and control group were given pure water interesting treatment from 29 th day,YXFM group was given Yixin-Fumai granules interesting treatment,the dose of the three groups were the same.During the period,the heart rate was monitored by electrocardiogram,and the general health status of mice in each group was recorded.After intragastric administration,the specimens were collected and made into sa node histological sections.HE staining and MASSON staining were performed to observe the pathological changes of SA node tissue and collagen fiber content,and to evaluate the improvement effect of YXFM on the function and tissue injury of SSS mice.The chemical constituents of Yixin-Fumai granules(except Maidong)were collected in TCMSP database,and the effective chemical constituents of Maidong were collected and supplemented in BATMAN-TCM database.All target information of drugs of YXFM collected was corrected by Uniprot.Using "Sick sinus syndrome" as the disease search term,human gene search was performed in Gene Cards,NCBI gene database and Dis Ge NET database to obtain potential targets.The intersection of drugs of YXFM-active ingredient-SSS target,PPI network model was constructed by String database,main targets were screened by topology analysis,gene clusters and core genes were obtained by MCODE clustering analysis,and the intersection targets were analyzed by KEGG and GO enrichment,and then utilized Cytoscape constructed the network model of "Drugs of Yixin-Fumai granules-active components-targets",and obtained the action mechanism and target of YXFM in treating SSS.Results:1.General health status: Mice in control group had slight hair removal at 28 days after surgery and 28 days after intragastric administration,and their overall health status was not abnormal.In the first 28 days of SSS group and YXFM group,the body activity,expression,fur,diet and other quality of life of mice decreased.The daily life of mice in YXFM group was intragastric from the beginning to the end,and the quality of life was gradually close to the control group.2.Heart rate monitoring: before modeling,there was no significant difference in heart rate among all groups(P>0.05).The heart rate of mice in the control group decreased to a certain extent after surgery,but the decrease was not different(P>0.05),and the heart rate of mice in the SSS and YXFM groups decreased gradually 28 days after surgery,with statistical significance(P<0.05).At the beginning of ingavage until day 28,the heart rate of SSS group still decreased gradually,while the heart rate of YXFM group increased gradually(P<0.05),while there was no statistical difference in the heart rate of control group(P>0.05).3.HE staining: In the control group,SAN tissue fibrosis was not obvious and was light blue.In SSS group,there was a large amount of blue staining in THE SAN area,which confirmed that THE SAN tissue was severely fibrotic and the collagen fiber content was the highest.SAN tissue of mice in YXFM group was similar to that in control group,showing light blue staining,and the degree of fibrosis was significantly lower than that in SSS group.4.MASSON staining: In the control group,SAN tissue fibrosis was not obvious,showing light blue;In SSS group,there was a large amount of blue staining in THE SAN area,which confirmed that THE SAN tissue was severely fibrotic and the collagen fiber content was the highest.SAN tissue of mice in YXFM group was similar to that in control group,showing light blue staining,and the degree of fibrosis was significantly lower than that in SSS group.5.Through computer network database,143 targets of YXFM and SSS were found.PPI network construction and topological analysis of the common targets showed that the main targets were IL-6,AKT1,IL1 B,CASP3 and MMP9,etc.Four gene clusters were identified by MCODE clustering analysis,and the three core targets were ICAM1,ESR1 and KCNA4.The key components of the drug and the network model of Drugs of Yixin-Fumai granules-active components-targets are shown in the attached figure.Conclusion:1.Yixin-Fumai granules can prevent SAN tissue fibrosis and improve sinoatrial node function in SAN injured mice.2.Network pharmacology study on the effect of Yixin-Fumai granules on SSS show the target information of YXFM to SSS and attain the network model of "Yixin-Fumai granules-active components-targets",and provided the main target including AKT1,CASP3,MMP9,ICAM1,etc.