基于“心脾同治”理论探究芍药苷改善阿霉素心脏毒性的效应机制  

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

作　　者：楚心雨 陈洁 吴雪芬 张倩[1] 程炜婷 位文佩 夏欢 夏桂阳 卫晓红 林生 CHU Xinyu;CHEN Jie;WU Xuefen;ZHANG Qian;CHENG Weiting;WEI Wenpei;XIA Huan;XIA Guiyang;WEI Xiaohong;LIN Sheng(Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京100700

出　　处：《中国中医基础医学杂志》2025年第4期621-626,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：中央高校基本科研业务费专项(2024-JYB-JBZD-046,2023-JYB-JBZD-048);国家自然科学基金项目(82430116,82073978)。

摘　　要：目的基于“心脾同治”理论,探究芍药苷改善阿霉素致小鼠心脏毒性的作用机制。方法选取雄性C57BL/6J小鼠40只,随机分为空白组、模型组、芍药苷组、右丙亚胺组,每组10只。空白组腹腔注射0.9%氯化钠溶液;模型组腹腔注射阿霉素(5mg/kg),每周1次,连续4周;芍药苷组先腹腔注射芍药苷(30mg/kg),30min后再给阿霉素,连续4周;右丙亚胺组先腹腔注射右丙亚胺(50mg/kg),30min后再给阿霉素。4周后,应用小动物超声评价各组心脏功能,HE染色观察心脏和脾脏的病理形态,ELISA检测血清中脑钠肽(BNP)、乳酸脱氢酶(LDH)水平,免疫组化染色和Western blot检测心脏和脾脏中巨噬细胞等指标的变化。结果与空白组比较,模型组小鼠左室射血分数(LVEF)和左室短轴缩短率(LVFS)均显著降低(P<0.05);血清BNP、LDH水平显著升高(P<0.05);HE染色可见心肌组织断裂,脾脏组织结构紊乱,红髓白髓界限模糊;心脏甘露糖受体1型(MRC-1,又称CD206)、CD11b、趋化因子受体2(CCR2)、Bcl-2相关X蛋白(Bax)表达水平显著升高,B淋巴细胞瘤-2(Bcl-2)表达水平显著降低(P<0.05)。脾脏抗原CD169、Bcl-2表达水平显著降低,Bax表达水平显著升高(P<0.05)。芍药苷组上述各项指标均有明显改善(P<0.05)。结论芍药苷可改善阿霉素致心脏毒性小鼠的心功能和脾脏损伤,其作用机制可能与芍药苷调节心脏的单核巨噬细胞趋化,调控心脾免疫反应稳态,从而抑制Bax/Bcl-2失衡相关。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

关 键 词：阿霉素 心脏毒性 心脾同治 芍药苷 巨噬细胞 

分 类 号：R285.5[医药卫生—中药学]