| Heart failure is a serious threat to human health which has caused all kinds of mental,organic and economic losses.Exploring effective medicines and new treatments for heart failure is an important focus of research.Bee venom compound preparation "Bao Yuan Ling"(BYL)is composed of 0.2%melittin,13?15%10-hydroxy-2-decanoic acid(royal jelly acid,10-HDA),20%propolis and 30%other lipids of royal jelly,dissolved in 70%ethanol.A previous study by our group found that BYL had significant curative effects on heart failure.On the basis of our results,with the combination of the defects in Chinese and western medicine and the high incidence and low cure rate of heart failure,in this study experimental animals(in vitro bullfrog hearts,mice with acute heart failure and rats with chronic heart failure)were administered with bee venom and its compound preparation BYL,the changes in the experimental animals before and after the treatment of bee venom and BYL were evaluated and analyzed with the data which included physical indexes,echocardiography,serum heart failure related remarkable indexes,myocardial pathological sections and expression profile microarray,in order to investigate the effects and mechanism of bee venom and its preparation on cardiac functions.The results revealed:1.Bee venom,with the positive inotropic effects similar to adrenaline,effectively enhanced contraction tension of bullfrog hearts in vitro,regulating effects of bee venom on cardiac functions were showed by the enhancement of bullfrog heart contractile force in vitro with appropriate doses;2.With low and medium doses of bee venom(0.5 mg/kg,1.5 mg/kg),serum BNP levels and organ coefficient were decreased,ventricular hypertrophy symptoms in acute heart failure mice induced by adriamycin were inhibited,heart failure processes were supressed,at the same time the heart rate and the myocardial cell injury of mice were reduced,the effects were similar to or even better than routine clinical medication of captopril;3.Rat models were established with chronic heart failure by long term injection with small doses of doxorubicin,with further research on the therapeutic effects of bee venom on the model rats,which proved that serum BNP,Tn-I,MYO/MB and CK-MB content and left atrial diameter,left ventricular end-systolic diameter,left ventricular end-diastolic diameter were reduced effectively after treated with bee venom.According to the results of expression profile microarray,compared with the model group,66 genes were up-regulated and 297 genes were down-regulated after the administration of bee venom,6 key genes including Smim5,Gimap,CyclinB2,UPF3B,Haptoglobin and FoxO were validated and analyzed,which provided experimental basis for the mechanism of bee venom on heart failure and exploration of new targeted sites on heart failure;4.Effects of BYL and its components on cardiac functions were also studied and discussed,the results showing that the contractile tension of bullfrog heart in vitro was improved with certain dosages of BYL and its components of royal jelly acid and propolis,cardiac functions were enhanced,and the working concentration of ethanol as the solvent had no negative effects on the heart.Meanwhile,physical indexes were improved,BNP,Tn-I,MYO/MB and CK-MB levels were decreased,the myocardial cell injury was reduced in chronic heart failure rats after BYL lavage.To sum up,bee venom and its compound preparation BYL improved cardiac functions of experimental animals,with all of the indexes comprehensively indicating that bee venom and BYL had therapeutic effects on heart failure,and worked in a similar way as the clinical medicine dexrazoxane,but the former had less toxic side effects,and the differences in gene expression level may be due to the different working pathways.This study explored the therapeutic effects of bee venom and its preparation BYL on heart failure,and concluded the possible mechanisms,providing a certain theoretical support for the application of bee venom and its preparations on heart failure. |
PDF Full Text Request