Establishment Of In Vitro Model Of Anti - Heart Failure And Screening Of Traditional Chinese Medicine Compounds

Heart failure (HF), often referred to as congestive heart failure (CHF), occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the body’s needs. The terms chronic heart failure or congestive cardiac failure (CCF) are often used interchangeably with congestive heart failure. The main content and results are as followed:1. Optimization of in titro culture on neonatal rat cardiomyocytes and human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs)neonatal rat cardiomyocytes and hiPS-CMs has been used as model and several culture condition has been optimized on RTCA, incuding base glue, glucose concentration, seeding number and cryopreservation. The results show the optimal condition were 1% matrigel, high glucose (30 mM) culture medium,17000 cells/well on Cardio E-Plate 96 well plate and fresh cardiomyocytes.2. Safety evaluation of 74 traditional Chinese medicine compounds on RTCA and exploratory analysisTo evaluate the cardiac safety,74 traditional Chinese medicine compounds were tested on neonatal rat cardiomyocytes. An exploratory analysis of beating pattern was established and further evaluated on neonatal rat cardiomyocytes and hiPS-CMs. The result shows 6 positive intrope compounds and 12 negatve intrope compounds were separated from 74 traditional Chinese medicine compounds. The current study clearly presents liensinine-and neferine-induced dose and time-dependant cardiotoxicity and neferine shows longer inhibition effect on both neonatal rat cardiomyocytes and hiPS-CMs.3. Verification of potential anti-heart failure compoundsTo evaluate the potential positive intrope effect compounds, ET-1 induced heart failure model was established on hiPS-CMs in this experiment. The contractile ability, heart failure-related gene NPPB, heart failure-related protein BNP expression were determined. The data suggested traditional Chinese medicine compound X25 has protective effect to ET-1 induced contractile dyfunction which was also inhibited the increasing expression of NPPB and BNP.