参麦注射液通过 miR-30a/Beclin 1 改善多柔比星心脏毒性。

Shenmai injection improves doxorubicin cardiotoxicity via miR-30a/Beclin 1.

机构信息

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of Traditional Research of TCM Prescription and Syndrome, Tianjin 300193, China.

出版信息

Biomed Pharmacother. 2021 Jul;139:111582. doi: 10.1016/j.biopha.2021.111582. Epub 2021 Apr 23.

DOI:10.1016/j.biopha.2021.111582

PMID:33895525

Abstract

BACKGROUND

Shenmai Injection (SMI) has been widely used in the treatment of cardiovascular diseases and can reduce side effects when combined with chemotherapy drugs. However, the potential protective mechanism of SMI on the cardiotoxicity caused by anthracyclines has not been clear.

METHODS

We used network pharmacology methods to collect the compound components in SMI and myocardial injury targets, constructed a 'drug-disease' target interaction network relationship diagram, and screened the core targets to predict the potential mechanism of SMI in treating cardiotoxicity of anthracyclines. In addition, the rat model of doxorubicin cardiotoxicity was induced by injecting doxorubicin through the tail vein. The rats were randomized in the model group, miR-30a agomir group, SMI low-dose group, SMI high-dose group，and the control group. The cardiac ultrasound was used to evaluate the structure and function of the rat heart. HE staining was used to observe the pathological changes of the rat myocardium. Transmission electron microscopy was used to observe myocardial autophagosomes. The expression of miR-30a and Beclin 1 mRNA in the rat myocardium was detected by RT-qPCR. Western Blot detected the expression of LC3-II/LC3-I and p62 protein.

RESULTS

The network pharmacological analysis found that SMI could act synergistically through multiple targets and multiple pathways, which might exert a myocardial protective effect through PI3K-Akt signaling pathways and cancer microRNAs. In vivo, compared with the control group, the treatment group could improve the cardiac structure and function, and reduce myocardial pathological damage and the number of autophagosomes. The expression of miR-30a in the myocardium of rats in miR-30a agomir group and SMI group increased (P < 0.01)，Beclin 1 mRNA was decreased (P < 0.01)，LC3-Ⅱ/LC3-I protein was decreased (P < 0.01 or P < 0.05)，and p62 protein was increased (P < 0.01 or P < 0.05).

CONCLUSIONS

SMI has the characteristics of multi-component, multi-target, and multi-pathway. It can inhibit myocardial excessive autophagy by regulating the expression of miR-30a/Beclin 1 and alleviate the myocardial injury induced by doxorubicin.

摘要

背景

参麦注射液（SMI）已广泛用于心血管疾病的治疗，与化疗药物联合使用时可降低副作用。然而，SMI 对蒽环类药物引起的心脏毒性的潜在保护机制尚不清楚。

方法

我们使用网络药理学方法收集 SMI 中的化合物成分和心肌损伤靶点，构建“药物-疾病”靶标相互作用网络图，并筛选核心靶标，预测 SMI 治疗蒽环类药物心脏毒性的潜在机制。此外，通过尾静脉注射阿霉素诱导大鼠阿霉素心脏毒性模型。将大鼠随机分为模型组、miR-30a 激动剂组、SMI 低剂量组、SMI 高剂量组和对照组。使用心脏超声评估大鼠心脏的结构和功能。HE 染色观察大鼠心肌的病理变化。透射电镜观察心肌自噬体。通过 RT-qPCR 检测大鼠心肌中 miR-30a 和 Beclin 1 mRNA 的表达。Western Blot 检测 LC3-II/LC3-I 和 p62 蛋白的表达。

结果

网络药理学分析发现，SMI 可以通过多个靶标和多个途径协同作用，可能通过 PI3K-Akt 信号通路和癌症 microRNAs 发挥心肌保护作用。在体内，与对照组相比，治疗组可改善心脏结构和功能，减少心肌病理损伤和自噬体数量。与对照组相比，miR-30a 激动剂组和 SMI 组大鼠心肌中 miR-30a 表达增加（P<0.01），Beclin 1 mRNA 表达降低（P<0.01），LC3-Ⅱ/LC3-I 蛋白表达降低（P<0.01 或 P<0.05），p62 蛋白表达升高（P<0.01 或 P<0.05）。