Characterization of TCM Syndromes and Expression of IRISIN in Mouse Model of Doxorubicin-Induced Chronic Heart Failure Based on Syndrome Differentiation by Formulas
Objective:To study the pathological characteristics of the mouse model of chronic heart failure (CHF) induced by doxorubicin (DOX) and evaluate the traditional Chinese medicine (TCM) syndromes and the expression characteristics of IRISIN based on syndrome differentia-tion by formulas.Methods:The mouse model was established by intraperitoneal injection of DOX at 5 mg/kg.The successfully modeled mice were assigned with the random number table method into model,Shenfu (参附) injection (9 mL/kg),Shenmai (参麦) injection (9 mL/kg),and Danhong (丹红) injection (6 mL/kg) groups.During the intervention period,mice in the model group and normal group were intraperitoneally injected with normal saline at a dose of 9 mL/kg.After modeling and drug intervention,the left ventricular ejection frac-tion (LVEF),left ventricular fractional shortening (LVFS),and stroke volume (SV) of mice in each group were recorded by Doppler echo-cardiography.After drug intervention,the expression levels of N-terminal-pro brain-derived natriuretic peptide (NT-pro BNP),creatine ki-nase-MB (CK-MB),and IRISIN in the serum and myocardium were measured,and the expression levels of CK-MB,IRISIN,B-cell lymphoma-2 (BCL-2),BCL-2-associated protein X (BAX),and Caspase 3 in the myocardium of the normal and model groups were determined.Hema-toxylin-eosin (HE) staining was used to observe the injury state of myocardial tissue in mice.Macroscopic characterization was employed to explore the TCM syndromes of the model and analyze the expression characteristics and significance of IRISIN in the model.Results:After drug intervention,compared with the normal group,the model group showed decreased LVEF,LVFS,and SV,up-regulated expression of NT-pro BNP and CK-MB and down-regulated expression of IRISIN in the serum,and up-regulated expression of CK-MB,BAX,and Caspase 3 and down-regulated expression of IRISIN and BCL-2 in the myocardial tissue (P<0.01 or P<0.05).Compared with the model group,Shenfu in-jection (9 mL/kg) increased the LVEF,LVFS,and SV,down-regulated the expression of NT-pro BNP and CK-MB and up-regulated the ex-pression of IRISIN in the serum,and up-regulated the expression of IRISIN and down-regulated the expression of CK-MB and NT-pro BNP in the myocardium (P<0.01 or P<0.05).Shenmai injection (9 mL/kg) decreased LVEF and LVFS,elevated the level of IRISIN in the ser-um,and down-regulated the NT-pro BNP expression and up-regulated the IRISIN expression in the myocardial tissue (P<0.01 or P<0.05).Danhong injection (6 mL/kg) decreased LVEF and LVFS and up-regulated the expression of NT-pro BNP and IRISIN in the myocardial tis-sue (P<0.01).The results of HE staining showed that the myocardial tissue of the normal group and the Shenfu injection (9 mL/kg) group was basically in a normal state,with regular and neatly arranged cardiomyocytes.Compared with the Shenfu injection (9 mL/kg) group,the model group,Shenmai injection (9 mL/kg) group,and Danhong injection (6 mL/kg) group showed mild or moderate myocardial injury,wavy myocardium,cell edema,mild vacuolar degeneration,and varying degrees of inflammatory cell infiltration and interstitial edema.Conclusion:Shenfu injection is an effective TCM preparation for treating DOX-induced CHF in the animal model,which may be related to the anti-myocar-dial apoptosis of IRISIN.Based on the theory of syndrome differentiation by formulas,it is hypothesized that the mouse model of DOX-induced CHF presents the Xinyangxu (心阳虚) syndrome.The low expression of IRISIN in the myocardial tissue is one of the biological characteris-tics of Xinyangxu.
Key word Shenfu (参附) injectionDoxorubicinChronic heart failureSyndrome differentiation by formulasTraditional Chinese medicine syndromeIRISIN
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