Based On CaN-NFAT3Signalling Pathways To Explore The Molecular Mechanism Of Sini Decoction And Active Component Of Aconite Root In Treatments Of Heart Failure Of Rats

Background and objectives:Chronic heart failure is extremely common clinical symptoms of critically. It is the ultimate outcome of cardiovascular disease. The signal molecular of CaN plays an important role in the process of heart failure. Recently, many studies show that the signal transduction pathway CaN-NFAT3leaded by the signal of CaN plays a key role in the process of heart failure. When heart failure occurs, CaN both in cardiac muscle tissue and peripheral blood increase in activity, which have a positive correlation with left ventricular hypertrophy.As the unique Ca2+/calmodulin dependent serine/threonine phosphatase calcineurin, CaN makes the dephosphorylation of nuclear factor of activated T cells(NFAT3), it also causes NFATc’s transport into the nuclear and then the transcription. The main physiological substrates are of vital importance in organism’s regulation function of immunization, nerves and cardiovascular systems, and the substrates including nuclear factor of activated T cells (NFAT3), IP3receptor, and inhibitor. The CHF was treated by poison Mao Xuan Hanako glycosides and othe cardiac glycoside drugs of Modern medicine. But the dose of treatment is extremely close to the dose of poisoning, and there is a large amount of side-effect on the organ. Many patients are often died of the side-effect of these drugs. Compared to modern medicine, TCM has special advantages, such as less side-effects significant effect on heart failure. Taking the advantages of TCM as the breakthrough point, the study uses the method of warming heart "yang"to research the curative effects of Sini decoction and fuzinoside on heart failure, and reveals the molecular mechacnism of the signal transduction CaN-NFAT3in the treatment of heart failure.Objective:To analyse the molecular mechacnism of the signal transduction CaN-NFAT3in the treatment of heart failure.Methods:One hundred sanitary grade SD rats were divided into control group (N=20) and model group (N=S0). Adriamycin was given intraperitoneally to copy the model of heart failure. The heart failure rats were divided into model group and Sini decoction group, Digoxigenin group, blank control group. Giving Sini decoction to the treatment groups for seven weeks, Model control group received the same volume of normal saline, positive control group was given digoxin,0.1mg/kg, once a day, for6weeks. CaM activity kit, calcium content kit, NFATc protein relatively express kit, Interleukin-2activity kit and Interleukin-4activity kit were used to detect the activity of CaN, the content of calcium,IL-2and IL-4, the expression of dephospho-NFAT3.Results:In the Sini decoction group, the indexes of hemodynamics in heart failure rats can be improved. The Sini decoction can protect cardiac muscle from degeneration necrosis and protect left ventricle from enlarging. Compared with mode group, the activity of CaN in Sini decoction was obviously lower(P<0.01). The calcium content was obviously lower(P<0.01).In the myocardial tissue, the light density ratio of dephosphorylation NFATc/(3-actin was lower than model group(P<0.01).Conclusions:The CaN-NFAT3signal transduction pathways may be suppressed, which can explain the key molecular mechanism of Sini decoction and fuzinoside in treatment of heart failure.