The Effect Of Simvastatin On Myocardial Apoptosis And The Discussion Of Its Mechanism In Chronic Heart Failure Rabbits

Part Ⅰ Effects of Simvastatin on cardiac function and serum IL-8、IL-33 and sST2 in Rabbits with Chronic Heart FailureObjective Observing chronic heart failure in rabbits,cardiac function and the levels of serum IL-8、IL-33 and sST2,and simvastatin effect on them.Method 36 male New Zealand big-eared rabbits were randomly divided into blank control group(CON group,n=12)and control group(ADR group,N=12),the ADR-s group(ADR-simvastatin group,ADR-s group,n=12),adaptive feed for a week,?both ADR group and ADR-s group were given concentration of 1.0 mg/ml doxorubicin solution,Ear marginal vein injection,Adriamycin dose of 1.5 mg/Kg,once a week,total of 12 weeks;?ADR-s group was given simvastatin mixed suspension(1.5mg/kg·d)intervention simultaneously;?CON group gived the same amount of saline respectively instead of adriamycin solution and simvastatin mixed suspension,a total of 12 weeks.After model established successfully,observed rabbit cardiac function by echocardiography examination and myocardial pathology change by HE staining and serum IL-18,IL-33,sST2 levels by ELISA.Results(1)Cardiac function change,the EF values of ADR-s group and ADR group were lower than the CON group(P<0.05),but the ADR-s group,s EF values are higher than ADR group,s(P< 0.05);(2)myocardial pathology change :compared with ADR group,ADR-s group myocardial cells arranged more neatly and there were less fibrous tissue hyperplasia(3)method of enzyme-linked immunosorbent(ELISA)to detect serum IL – 18、 IL – 33、 sST2,CHF –s and ADR group serum level of IL-18 were higher than the CON group(P<0.05),ADR group,s was higher than ADR-s group,s(P<0.05);serum IL – 33 level of ADR-s group was obviously higher than other two groups(P <0.05);Both ADR-s group and ADR group serum sST2 levels were higher than CON group,(P<0.05),but ADR-s group,s was lower than ADR group,s(P<0.05).Conclusion simvastatin protected cardiac function of chronic heart failure in rabbits,inhibiting myocardial remodeling and,its possible mechanism was associated with regulating inflammatory cytokines IL-18,IL-33 expression levels.Part Ⅱ Effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in Rabbits with Chronic Heart FailureObjective Observing effects of simvastatin on myocardial apoptosis and oxidative stress mechanism in rabbits with chronic heart failure.Methods The methods are the same as the part Ⅰ.Echocardiography examination were performed at 13 th week,MASSON staining to detect myocardial fibrosis degree,detecting myocardial apoptosis by TUNEL,colorimetry to detect myocardial superoxide dismutase(SOD),malondialdehyde(MDA),ELISA to detect serum b-type brain natriuretic peptide(BNP)level.Results(1)cardiac function,ADR and ADR-s group EF value were lower than CON group(P<0.05),but the ADR group was lower than the ADR-s group(P<0.05);(2)MASSON staining: compared with ADR group,there was less myocardial cell hyperplasia of fibrous tissue in ADR-s group.(3)mycardial apoptosis: apoptosis positive cells of CON group was less than the ADR group and ADR-s,and ADR-s group less than ADR group,;the apoptosis index,CON group was less than ADR and ADR-s group,ADR-s group was less than ADR group(P<0.05).(4)myocardial cell SOD activity and MDA content: compared with ADR group,SOD activity of ADR-s group was higher and MDA content was lower(P<0.05).(5)serum BNP level: ADR and ADR-s group serum BNP level were higher than the CON group,ADR group was higher than ADR-s group(P<0.05).Conclusion: simvastatin can protect cardiac function of rabbits with chronic heart failure,the possible mechanism was,strengthened myocardial SOD activity and reduce cell lipid peroxidation,inhibiting myocardial apoptosis and against myocardial remodeling.