麝香通心滴丸通过下调 APOC1 抑制 STAT3 信号通路减轻冠状动脉微栓塞引起的心肌损伤。

Shexiang tongxin dropping pill alleviates myocardial injury induced by coronary microembolization by down-regulating APOC1 to inhibit STAT3 signaling pathway.

机构信息

Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China.

出版信息

Aging (Albany NY). 2024 May 20;16(10):8484-8496. doi: 10.18632/aging.205796.

DOI:10.18632/aging.205796

PMID:38771126

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11164485/

Abstract

AIM

This study determines to validate the mechanism of Shexiang Tongxin dropping pill (STDP) in attenuating coronary microembolization (CME) induced myocardial injury.

METHODS

CME rat models were established and underwent corresponding treating. Gene chip analysis was performed in rat myocardial tissues for GO and KEGG enrichment analysis. The differentially expressed genes were detected by qRT-PCR. H&E staining and ELISA were used for pathological analysis and detection of troponin (cTnI) and Creatine Kinase Isoenzyme (CK-MB). Lipopolysaccharide (LPS) treated primary cardiomyocytes were used to mimic inflammatory models. Cell viability and apoptosis of cardiomyocytes were determined by MTT and flow cytometry. The expressions of inflammatory cytokines, apoptotic proteins and proteins related to the STAT3 signal pathway were detected by western blot. APOC1 mRNA expression was detected by qRT-PCR. Immunofluorescence (IF) was used for subcellular localization of p-STAT3 and the binding of APOC1 with STAT3 was verified using Co-IP.

RESULTS

STDP can attenuate myocardial injury in CME rat models, and lead to decreased expression of APOC1 and suppressed STAT3 signal pathway. models found STDP can suppress the cell viability and cell apoptosis of primary cardiomyocytes, in addition to suppressing the secretions of IL-6, IL-1β and TNF-α, while the protective effect of STDP can be reversed by overexpression of APOC1. Co-IP found that APOC1 can bind STAT3 directly. APOC1 can increase p-STAT3 expression in the nucleus to activate the STAT3 signal pathway.

CONCLUSIONS

STDP can suppress APOC1 and STAT3 signal pathway to inhibit inflammation and cell apoptosis of cardiomyocytes. APOC1 may be one of the key regulatory factors in CME-induced myocardial injury.

摘要

目的

本研究旨在验证麝香通心滴丸（STDP）减轻冠状动脉微栓塞（CME）引起心肌损伤的作用机制。

方法

建立 CME 大鼠模型并进行相应处理。对大鼠心肌组织进行基因芯片分析，进行 GO 和 KEGG 富集分析。通过 qRT-PCR 检测差异表达基因。进行 H&E 染色和 ELISA 检测肌钙蛋白（cTnI）和肌酸激酶同工酶（CK-MB）。用脂多糖（LPS）处理原代心肌细胞模拟炎症模型。通过 MTT 和流式细胞术测定心肌细胞活力和凋亡。通过 Western blot 检测炎症细胞因子、凋亡蛋白和 STAT3 信号通路相关蛋白的表达。通过 qRT-PCR 检测 APOC1 mRNA 的表达。用免疫荧光（IF）检测 p-STAT3 的亚细胞定位，并通过 Co-IP 验证 APOC1 与 STAT3 的结合。

结果

STDP 可减轻 CME 大鼠模型的心肌损伤，导致 APOC1 表达下调，抑制 STAT3 信号通路。在体外实验中，我们发现 STDP 可抑制原代心肌细胞的活力和凋亡，同时抑制 IL-6、IL-1β和 TNF-α的分泌，而过表达 APOC1 可逆转 STDP 的保护作用。Co-IP 发现 APOC1 可直接与 STAT3 结合。APOC1 可增加核内 p-STAT3 的表达，激活 STAT3 信号通路。