The Studies Of The Mechanism Of Aconiti Lateralis Radix In The Treatment Of Rats With Acute Heart Failure Based On The Transriptional Analysis

Aconite is a processed product of Aconitum carmichaelii Debx.,which is one of the commonly used drugs in Wenli medicine.It is first published in Shennong Bencao,and is called"the best one among 100 medicines,"Which is also called“the first choice used to save the starvation of Yang.”In order to further study the molecular mechanism about how aconite stronges heart,in this study,we made a rat model of acute heart failure by propafenone,and used high-throughput transcriptome sequencing technology to transcribe and sequence the myocardial tissue of heart failure rats.The expression of all genes,through functional annotation,enrichment analysis and differential expression genes screening,locate the key genes and signaling pathways related to acute heart failure in the treatment of acute heart failure,in order to explain the molecular mechanism of aconite treatment of acute heart failure transcriptionally.Methods:1.The heart rate and intraventricular pressure of healthy adult rats were monitored by left ventricular intubation.The acute heart failure model was prepared by injection of propafenone hydrochloride into the femoral vein.After successful modeling,the rats in each group were administered:The positive drug-administered group was given Shenfu injection(3.3 mL·kg^-1),the model group was given distilled water 0.1 mL·kg-1,and the drug-administered group was given aconite decoction(1.25 g·kg^-1,2.50 g·kg^-1g,5.00 g·kg^-1).The changes of HR,+LV dp·dtmax^-11 and-LV dp·dtmax^-11 at 5,10,20,30,60 min before and after modeling were recorded.Another batch of rats was taken,and the rats with acute heart failure were administered in the same manner.After 20 minutes of administration,the rats in each group were subjected to abdominal aorta blood collection,and the serum was determined by enzyme-linked immunosorbent assay?Elisa?.The levels of various cytokines?Ang-II,TNF-?,BNP,ANP,ALD?and their activity changes.The myocardial tissues of the rats in the blank group,the model group and the Fuzi decoction administration group were used as experimental materials,and a total RNA extraction-reverse transcription-cDNA text database was constructed,and high-throughput sequencing was performed by HiSeq X-ten platform.,a database of transcriptome samples of rat myocardial tissue was constructed.Through GO function annotation,DEG analysis,KEGG enrichment analysis and expression difference analysis process,candidate key genes and signal pathways for aconite treatment of heart failure were screened.The transcriptional activity of the mRNA expression level of some candidate genes screened in the previous step was verified by real-time PCR?QRT-PCR?.Results:1.Rats after propafenone modeled,HR and+LVdp·dtmax^-1,-LVdp·dtmax^-1values??decreased,Aconite decoction 1.25 g·kg^-1,2.50 g·kg^-11 5.00 g·kg^-11 duodenal administration can effectively increase HR,+LVdp·dtmax^-11 and-LVdp·dtmax^-11 in model rats,while Ang-II,ANP,BNP in serum ALD,TNF-?and other indicators have been reduced.High-throughput RNA-seq sequencing obtained 227,662,430 high-quality base sequences with 67,974,816,306 bp bases and 90.32%Q30.The ratio of Reads to reference genomes of each sample was 93.02%⁹3.47%.Wait,there is a higher comparison.3.Under the differential expression gene screening criteria of FDR...