Mechanism of Paeoniflorin in the Treatment of Doxorubicin Cardiotoxicity Based on"Heart-Spleen Co-Treatment"Theory

CHU Xinyu; CHEN Jie; WU Xuefen; ZHANG Qian; CHENG Weiting; WEI Wenpei; XIA Huan; XIA Guiyang; WEI Xiaohong; LIN Sheng

doi:10.3969/j.issn.1006-3250.2025.4.zgzyjcyx202504014

Abstract：Objective To explore the effect and mechanism of Paeoniflorin(PF)in ameliorating doxorubicin(DOX)cardiotoxicity in mice based on the theory of"heart-spleen co-treatment".Methods Forty male C57BL/6J mice were randomly divided into four groups(n=10):Control group,DOX group,PF+DOX group,and dexrazoxane+DOX(DZR+DOX)group.Control group received intraperitoneal injection of 0.9%sodium chloride solution.DOX group were established through intraperitoneal injection of DOX(5 mg/kg,once a week,for 4 weeks).In the PF+DOX group,the mice were first intraperitoneally injected with PF(30 mg/kg),and then given DOX after 30 minutes for 4 consecutive weeks.The DZR+DOX group was first injected with DZR(50 mg/kg),then given DOX after 30 minutes.After 4 weeks,cardiac function was assessed using echocardiography.The pathological morphology of heart and spleen tissue was evaluated by HE staining.The expression levels of serum BNP and LDH were measured by ELISA.The variation of macrophage-related indicators in heart and spleen were determined by Western blot and Immunohistochemistry.Results Compared with the control group,the LVEF and LVFS values were significantly decreased(P<0.05),as well as the serum BNP and LDH contents were significantly increased in mice of the DOX group(P<0.05).According to HE staining,extensive myocardial tissue fracture was observed,and the spleen structure was disordered in DOX group compared with Control group.In addition,the boundaries of the red medulla and white medulla were blurred.The expression of CD206,CD11b,CCR2 and Bax in the heart was significantly increased,Bcl-2 was significantly decreased(P<0.05).And the expressions of CD169 and Bcl-2 in the spleen were significantly decreased,Bax was significantly increased(P<0.05).The above indicators were improved in the PF+DOX group.Conclusion PF can improve the cardiac function and spleen damage in mice with DOX cardiotoxicity,and its mechanism may be related to the regulation of monocyte macrophage chemotaxis in the heart and modulated the homeostasis of immune responses between the heart and spleen,thereby inhibiting Bax/Bcl-2 imbalance.