| Backgrounds and Objectives:Heart failure is the end stage of various cardiovascular diseases development, hasbecome one of the three big diseases in cardiovascular field in21st century. Study on thedevelopment of new drugs that efficient, safe and suitable for clinical treatment isimportant. Myocardial diseases or others impair heart function by causing excessive heartstress, the body compensates heart function through a variety of adjustment mechanisms,experiences fully compensated, not fully compensated and decompensated phases,eventually occurs heart failure. Danshensu is one of the main water-soluble activeingredients of salvia miltiorrhiza, researches show Danshensu has a significant protectiveeffect in the cardiovascular system, againsts myocardial ischemia and hypoxia, myocardialischemia reperfusion injury, cardiac hypertrophy, arrhythmia, thrombus and coronaryartery dilatation. Due to the development of modern medical technology, survival rate isgreatly increased in patients with acute myocardial infarction, but the damage continued, alot of patients with acute myocardial infarction transform chronic heart failure. SodiumDanshensu has a protective effect on acute myocardial infarction, but the study on chronicheart failure is rare. Sodium Danshensu is not only used in clinical treatment of acutemyocardial infarction, but also used in the prognosis of myocardial infarction. This topicwill study on the effects of Sodium Danshensu in chronic heart failure and explore thepossible mechanisms of prevention and treatment of heart failure, provide a theoretical andexperimental basis for sodium danshensu resist chronic heart failure, provide a scientificbasis for further development and utilization of sodium danshensu.Methods:1Myocardial infarction was induced by ligation of left coronary artery in rats andthen established chronic heart failure model, the survival rats after operation wererandomly divided into7groups, including sodium Danshensu low, medium and highgroups (12,24,48mg/kg·d, iv and ip in turn), captopril group (15mg/kg·d, ig) and Dansheninjection group (1.2g/kg·d, iv and ip in turn), model group and sham group. Model groupand sham group received saline, continuous administration for8weeks.2The rats were randomly divided into6groups, including sodium Danshensu low,medium and high groups (24,48,96mg/kg·d, iv) and Danshen injection group (2.4g/kg·d,iv), model group and sham group. Model group and sham group received saline,pre-administered for4days. Myocardial infarction was induced by ligation of left coronary artery in rats and then established early heart failure model, continuous administration for10days.3The heart function of early heart failure rats and chronic heart failure rats weredetected by echocardiography, microstructure and ultrastructure of myocardium in chronicheart failure rats were observed by HE staining and transmission electron microscopy.4CX43, Bcl-2, Bax mRNA expression of myocardium in early heart failure rats weredetected by Real-Time PCR.5MMP-9, TIMP-1mRNA expression of myocardium in chronic heart failure ratswere detected by Real-Time PCR; Bcl-2, Bax protein expression of myocardium in chronicheart failure rats were detected by Western Blot.6EPCs were separated from bone marrow in chronic heart failure rats, detected itsmigration, adhesion and tubule formation function.Results:1Echocardiography showed left ventricular ejection fraction and left ventricularfractional shortening significantly reduced in heart failure rats (P<0.01vs contrl), sodiumDanshensu can increased EF and FS in early heart failure rats (P<0.05vs Model) andchronic heart failure rats. Cardiac pathology and electron microscopy examination showedsodium Danshensu can improved microstructure and ultrastructure of myocardium inchronic heart failure rats.2Real-Time PCR showed CX43mRNA (P<0.05vs ctrl), Bcl-2/Bax mRNA (P<0.01vs ctrl) expression of myocardium significantly reduced in early heart failure rats, sodiumDanshensu can elevated CX43mRNA (P<0.01vs CHF), Bcl-2/Bax mRNA (P<0.01vsCHF) expression of myocardium.3Real-Time PCR showed MMP-9mRNA expression of myocardium significantlyreduced in chronic heart failure rats (P<0.01vs ctrl), sodium danshensu can reducedMMP-9mRNA (P<0.01vs CHF), elevated TIMP-1mRNA (P<0.05vs CHF) expression ofmyocardium; Western Blot showed Bcl-2/Bax protein expression of myocardiumsignificantly reduced in chronic heart failure rats(P<0.01vs ctrl), sodium Danshensu canelevated Bcl-2/Bax protein expression of myocardium (P<0.01vs CHF); migration,adhesion and tubule formation experiments showed the EPCs function significantlyreduced in chronic heart failure rats (P<0.01vs ctrl), sodium Danshensu can increased theEPCs function (P<0.01vs CHF).Conclusions: 1Sodium Danshensu can rises left ventricular ejection fraction and left ventricularfractional shortening in early heart failure and chronic heart failure rats, improvesmicrostructure and ultrastructure of myocardium in chronic heart failure rats, has aprotective effect on chronic heart failure.2Sodium Danshensu can elevates CX43, Bcl-2/Bax mRNA expression ofmyocardium in early heart failure rats, reduces MMP-9mRNA and elevates TIMP-1mRNA expression of myocardium in chronic heart failure rats; Sodium Danshensu canelevates Bcl-2/Bax protein expression of myocardium in chronic heart failure rats; elevatesmigration, adhesion and tubule formation function of EPCs in chronic heart failure rats.The mechanisms of sodium Danshendu againsts heart failure may affect gap junction,inhibit cardiomyocyte apoptosis, suspend ventricular remodeling, protect and elevate thefunction of EPCs etc. |
PDF Full Text Request