Mechanism of Shuxuening Injection Inhibiting Excessive Mitochondrial Fission and Apoptosis Alleviating Doxorubicin-induced Cardiotoxicity
Objective:To investigate the effect and possible mechanism of Shuxuening injection on doxorubicin-induced cardiotoxicity.Methods:Forty-eight Sprague-Dawley male rats were randomly divided into blank group,doxorubicin group,low-dose Shuxuening injection group and high-dose Shuxuening injection group,with 12 rats in each group.The blank group was intraperitoneally injected with normal saline,doxorubicin group was intraperitoneally injected with doxorubicin 2 mg/kg,low-dose Shuxuening injection group was intraperitoneally injected with doxorubicin 2 mg/kg and Shuxuening injection 1 mL/kg;high-dose Shuxuening injection group was intraperitoneally injected with doxorubicin 2 mg/kg and Shuxuening injection 2 mL/kg.The heart injury model was established after intervention once a day for 7 days.The hemodynamic indexes of rats in each group were detected.The pathological changes of myocardial tissue were observed.Serum troponin T(cTnT)and protein expression levels of B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved Caspase-3,phospho-dyne-associated protein-1(Drp1),and optic atrophy associated protein 1(OPA1)were detected.Results:Compared with the blank group,the maximum rate of left ventricular pressure rise(+dp/dtmax)and the absolute values of maximum rate of left ventricular pressure fall(-dp/dtmax)in the doxorubicin group decreased(P<0.01),muscle fibers were broken and arranged disorderly,the content of cTnT in serum increased(P<0.01),the protein expressions of cleaved Caspase-3,Bax and p-Drp1 increased(P<0.01),and the protein expressions of Bcl-2 and OPA1 decreased(P<0.01).Compared with the doxorubicin group,the cardiac function and structure of the rats in the Shuxuening injection group improved(P<0.01),the serum cTnT level decreased(P<0.01),and the expressions of cleaved Caspase-3,Bax and p-Drp1 decreased(P<0.05 or P<0.01),the expression of Bcl-2 and OPA1 increased(P<0.05 or P<0.01).Conclusion:Shuxuening injection may alleviate doxorubicin-induced cardiotoxicity by inhibiting excessive mitochondrial fission and apoptosis
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维普
