| Objective:Doxorubicin is the first-line anticancer drug in clinical cancertreatment program,but its cardiac toxicity limit its using.This experiment copythe doxorubicin-induced myocardial injury model,give different concentrationsof the pseudo-ginsenoside GQ (PGQ),explore the protective effect of PGQ onacute drug-induced myocardial injury in rats..Methods:Wistar male rats were randomly divided into six groups(n=5):①normal control group:each rat was injected intravenously an equal volume ofsaline on1-7days,and each shared intravenous volume of saline on the fifthday of the experiment;②The doxorubicin group:each rat was injected an equalvolume of saline in tail vein on1-7days,and each was injected in femoral veinof18mg/kg of doxorubicin on the fifth day of the experiment;③Doxorubicin+dexrazoxane group:each rat was injected an equal volume ofsaline in tail vein on the1-4,6-7days,and each was injected180mg/kg ofdexrazoxane in the femoral vein through vein catheter on the fifth day,then1%heparin sealed tube,finally each was injected18mg/kg of doxorubicin30minafter the dexrazoxane;④Doxorubicin+PGQ (low dose) group:each rat wasinjected an volume of3mg/kg of the PGQ,and each was injected in femoralvein of18mg/kg of doxorubicin on the fifth day after PGQ;⑤Doxorubicin+PGQ (medium dose) groups: each rat was injected an volume of6mg/kg of the PGQ,and each was injected in femoral vein of18mg/kg ofdoxorubicin on the fifth day after PGQ;⑥Doxorubicin+PGQ (high dose) group:each rat was injected an volume of12mg/kg of the PGQ,and each was injectedin femoral vein of18mg/kg of doxorubicin on the fifth day after PGQ.Each ratwas measured the weight on the eighth day,and each was detected cardiac function,tested serum TnI level,calculated the heart/body weight ratio,observedmorphological and ultrastructural changes of myocardial tissue,and analyzedstatistically.Results:①There is no significant difference of the total decline weight indexrazoxane group and low dose PGQ group compared with doxorubicinmodel group. The total decline weight is significantly reduced with significantdifferences (P<0.05) in medium and high dose PGQ group compared withmodel group,and there is no significant difference with the normal controlgroup.The total decline weight is significantly reduced with significantdifferences (P<0.05) in medium and high dose PGQ group compared withdexrazoxane group;②HR,LVSP and±dp/dtmaxdecrease significantly withsignificant difference (P<0.05) in doxorubicin model group compared withnormal control group.LVSP and±dp/dtmaxare significantly increased withsignificant difference (P<0.05) in dexrazoxane group compared withdoxorubicin model group,and there is no significant difference with the normalcontrol group.LVSP and±dp/dtmaxare significantly increased with significantdifference (P<0.05) in medium and high dose PGQ group compared withdoxorubicin model group,and there is no significant difference with the normalcontrol and dexrazoxane group. There is no significant difference between lowdose PGQ group and normal control group;③TnI levels of doxorubicin modelgroup are significantly increased compared with normal control group withsignificant difference (P<0.05).TnI levels are significantly decreased withsignificant difference (P<0.05) in dexrazoxane group compared withdoxorubicin model group,and there is no significant difference with the normalcontrol group. TnI levels are significantly decreased with significant difference(P<0.05) in medium dose PGQ group compared with doxorubicin modelgroup,and there is no significant difference with the normal control anddexrazoxane group. There is no significant difference between low dose PGQ group,high dose PGQ group and normal control group;④Heart/body weightratio (HW/BW) increase significantly with significant difference (P<0.05) indoxorubicin model group compared with normal control group. HW/BW aresignificantly decreased with significant difference (P<0.05) indexrazoxane group compared with doxorubicin model group,and there is nosignificant difference with the normal control group.HW/BW are significantlydecreased with significant difference (P<0.05) in medium and high dose PGQgroup compared with doxorubicin model group,and there is no significantdifference with the normal control and dexrazoxane group. There is nosignificant difference between low dose PGQ group and normal control group;⑤The dexrazoxane group,low dose PGQ group,medium dose PGQ group andhigh dose PGQ group improve the morphological changes of the myocardialtissue,and vacuoles degeneration of myocardial tissue are significantly reducedcompared with the doxorubicin model group.Medium dose PGQ group lesionsare reduced the most obvious among them;⑥Medium dose PGQ groupsignificantly improve the ultrastructural changes of myocardial cells comparedwith the doxorubicin model group and dexrazoxane group.Conclusion:①The establishment of acute cardiac toxicity model throughthe femoral vein injection of doxorubicin is to study the protective effect ofPGQ in cardiotoxicity;②Medium dose (6mg/kg) PGQ and high dose (12mg/kg)PGQ can improve the general condition of the rats and significantly reducethe weight of the total decline weight;③Medium dose (6mg/kg) PGQ and highdose (12mg/kg) PGQ can significantly improve the cardiac function ofdoxorubicin-induced myocardial injury;④Medium dose (6mg/kg) PGQ cansignificantly reduce the TnI level of doxorubicin-induced myocardial injury;⑤Medium dose (6mg/kg) PGQ and high dose (12mg/kg) PGQ can significantlyreduce the rat heart/body weight ratio,thus improve the degree of heart failure in rats;⑥Medium dose (6mg/kg) PGQ can significantly improve themorphological abnormalities and ultrastructural changes of doxorubicin-induced myocardial injury. |
PDF Full Text Request