■艾迪注射液(ADI),中药抗肿瘤注射剂,通常与多柔比星(DOX)联合用于治疗恶性肿瘤。临床应用ADI可改善DOX的心脏毒性。然而,相关机制未知。
■探讨ADI对DOX诱导的心脏毒性的影响及其机制。
■ICR小鼠随机分为六组:对照组,ADI-L,阿迪-H,DOX,DOX+ADI-L和DOX+ADI-H.DOX(i.p.,在存在或不存在ADI的情况下施用0.03mg/10g)(i.p.,0.1或0.2mL/10g)连续两周。心脏病理学和AST水平,LDH,CK,评估CK-MB和BNP。在存在或不存在ADI(1、4、10%)的情况下用DOX处理H9c2细胞。细胞活力,caspase-3活性,核形态,然后评估CBR1表达。心脏中的DOX和阿霉素(DOXol)浓度,肝脏,肾脏,血清,并通过UPLC-MS/MS分析细胞。
■大剂量ADI显著降低DOX引起的病理变化和AST水平,LDH,CK,CK-MB和BNP至正常。与ADI(1,4,10%)联合处理提高了细胞活力,IC50从68.51μM(单独的DOX)增加到83.47、176.9和310.8μM,caspase-3活性分别降低39.17、43.96和61.82%,分别。大剂量ADI抑制了32.3%的CBR1蛋白表达,降低心脏中的DOXol水平,血清和H9c2细胞分别为59.8、72.5和48.99%,分别。
■ADI通过抑制CBR1表达降低DOX诱导的心脏毒性,为合理使用ADI提供了科学依据。
UNASSIGNED: Aidi injection (ADI), a traditional Chinese medicine antitumor injection, is usually combined with doxorubicin (DOX) for the treatment of malignant tumours. The cardiotoxicity of DOX is ameliorated by ADI in the clinic. However, the relevant mechanism is unknown.
UNASSIGNED: To investigate the effects of ADI on DOX-induced cardiotoxicity and its mechanism.
UNASSIGNED: ICR mice were randomly divided into six groups: control, ADI-L, ADI-H, DOX, DOX + ADI-L and DOX + ADI-H. DOX (i.p., 0.03 mg/10 g) was administered in the presence or absence of ADI (i.p., 0.1 or 0.2 mL/10 g) for two weeks. Heart pathology and levels of AST, LDH, CK, CK-MB and BNP were assessed. H9c2 cells were treated with DOX in the presence or absence of ADI (1, 4, 10%). Cell viability, caspase-3 activity, nuclear morphology, and CBR1 expression were then evaluated. DOX and
doxorubicinol (DOXol) concentrations in heart, liver, kidneys, serum, and cells were analysed by UPLC-MS/MS.
UNASSIGNED: High-dose ADI significantly reduced DOX-induced pathological changes and the levels of AST, LDH, CK, CK-MB and BNP to normal. Combined treatment with ADI (1, 4, 10%) improved the cell viability, and IC50 increased from 68.51 μM (DOX alone) to 83.47, 176.9, and 310.8 μM, reduced caspase-3 activity by 39.17, 43.96, and 61.82%, respectively. High-dose ADI inhibited the expression of CBR1 protein by 32.3%, reduced DOXol levels in heart, serum and H9c2 cells by 59.8, 72.5 and 48.99%, respectively.
UNASSIGNED: ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.