Study On Protective Effects Of Pseudo-Ginsenoside GQ On Doxorubicin-induced Chronic Myocardial Damage In Rats

Objective:Doxorubicin is widely used in clinical as anticancer drug, thecumulative cardiac toxicity in patients limits its long-term application. Inthis study, we form the model of doxorubicin-induced chronicmyocardial damage in rat, and supply3different doses ofpseudo-ginsenoside GQ (PGQ), explore the protective effect of PGQ onDoxorubicin-induced chronic myocardial damage in Rats.Methods:60Wistar Male rats weighing140-160g were divided into6groupsrandomly (n=10).①normal control group (CONTROL group): Eachrat was injected intravenously an equal volume of saline for3days.On thethird day of the experiments, intravenous injection of saline was repeated30min later after previous intravenous injection of an equal volume ofsaline;②doxorubicin group (DOX group): Each rat was injectedintravenously an equal volume of saline for3days.On the third day of theexperiments,3mg/kg of doxorubicin was injected again30min laterafter previous intravenous injection of an equal volume of saline;③doxorubicin+dexrazoxane group ([DOX+DZR] group): Each rat wasinjected intravenously an equal volume of saline for2days.On the thirdday of the experiments,60mg/kg of dexrazoxane was injected and3mg/kg of doxorubicin was injected30min later after previous injection;④doxorubicin+low-dose of pseudo-ginsenoside GQ group (DOX+ PGQ [L] group): Each rat was injected intravenously3mg/kg of PGQfor3days.On the third day of the experiments,3mg/kg of doxorubicinwas injected30min later after previous injection;⑤doxorubicin+medium-dose of pseudo-ginsenoside GQ group (DOX+PGQ [M]group):Each rat was injected intravenously6mg/kg of PGQ for3days.On the third day of the experiments,3mg/kg of doxorubicin wasinjected30min later after previous injection;⑥doxorubicin+high-doseof pseudo-ginsenoside GQ group (DOX+PGQ [H] group): Each ratwas injected intravenously12mg/kg of PGQ for3days.On the third dayof the experiments,3mg/kg of doxorubicin was injected30min later afterprevious injection。Through6weeks of continuous administration, thecondition of rats were observed during the experiment carefully, changesin body weight of rats were recorded weekly. On the7th week ofexperiment，detected cardiac function,tested serum TnI and BNP levels,measured values of weight change、mortality、heart weight、heart/bodyweight ratio,ultrastructural and morphological changes of myocardialtissue was observed, and analyzed statistically.Results:1) After6weeks of continuous administration，the mortality ofDOX group was40%, the models of heart failure were formed insurvival rats. During the experiment,the conditions of DOX group werepoor,some rats appeared with bleeding in muzzle, eyelids andextremities skin. The average weights of rats were inhibited severely,with an increase of21.5%, the average weights of rats of CONTROLgroup increased143.4%. Cardiac function of DOX group results of HR,BP, LVSP,±dp/dt max were significantly reduced, serum TnI and BNPlevels were significantly elevated and heart weights were significantly reduced compared with CONTROL group with significant difference(P<0.05). Tissue morphology and ultrastructure showed severe damage,obvious cytoplasmic vacuoles and segmental cohesion and dissolutionwere observed, ultrastructural shows muscle fibers dissolved, vacuolardegeneration of mitochondria.2)The mortality of [DOX+DZR] group was10%, with an averageweight increase of64.8%. Cardiac function、 serum TnI and BNP levelsand heart weight were significantly elevated compared with DOX groupwith significant difference (P<0.05),there was no significant differencewith the CONTROL group （P>0.05）.The damage of morphology andultrastructure was significantly reduced.3) The mortality of DOX+PGQ [H] group (12mg/kg) was20%,with an average weight increase of62.0%. The conditions of rats werebetter than DOX group. Cardiac function、 serum TnI and BNP levelsand heart weight were significantly elevated compared with DOX groupwith significant difference (P<0.05), there was no significant differencewith the CONTROL group and [DOX+DZR] group（P>0.05）.Thedamage of morphology and ultrastructure was reduced.4)The mortality of DOX+PGQ [L] group (3mg/kg) and DOX+PGQ [M] group (6mg/kg) were30%and40%, with an average weightincrease of56.8%and32.5%, the conditions of rats were better thanDOX group. There was no improvement of Cardiac function、serum TnIand BNP levels and heart weight compared with DOX group,with nosignificant difference （P>0.05）, and with significant difference with theCONTROL group and [DOX+DZR] group and DOX+PGQ [H] group(12mg/kg)(P<0.05).There was no significant improvement of damage ofmorphology and ultrastructure. Conclusion:1、The administration of cumulative doses of doxorubicin can leadto inhibition of weight increase, Cardiac function of DOX group resultsof HR, BP, LVSP,±dp/dt max were significantly reduced,serum TnIand BNP levels were significantly increased and heart weight wassignificantly reduced, ultrastructural and morphological of myocardialtissue showed severe damage.All above shows doxorubicin lead to severemyocardial cell damage.2、The application of dose of12mg/kg PGQ significantly reducesdoxorubicin-induced chronic myocardial damage in Rats. Its protectiveeffect of myocardial cell is as well as dexrazoxane.3、 PGQ may become a new cardioprotective drugs used asprevention of doxorubicin-induced myocardial damage.