Tasly Microcirculation Research Center, Peking University Health Science Center, Haidian District, Beijing 100191, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Haidian District, Beijing 100191, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Haidian District, Beijing 100191, China; Beijing Laboratory of Integrative Microangiopathy, Haidian District, Beijing 100191, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Haidian District, Beijing 100191, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Haidian District, Beijing 100191, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Haidian District, Beijing 100191, China; Beijing Laboratory of Integrative Microangiopathy, Haidian District, Beijing 100191, China; Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Haidian District, Beijing 100191, China.
Phytomedicine. 2022 Nov;106:154405. doi: 10.1016/j.phymed.2022.154405. Epub 2022 Aug 23.
Stent implantation has been increasingly applied for the treatment of obstructive coronary artery disease, which, albeit effective, often harasses patients by in-stent restenosis (ISR).
The present study was to explore the role of compound Chinese medicine Cardiotonic Pills® (CP) in attenuating ISR-evoked myocardial injury and fibrosis.
Chinese miniature pigs were used to establish ISR model by implanting obsolete degradable stents into coronary arteries. Quantitative coronary angiography (QCA) was performed to confirm the success of the model.
CP was given at 0.2 g/kg daily for 30 days after ISR. On day 30 and 60 after stent implantation, the myocardial infarct and myocardial blood flow (MBF) were assessed. Myocardial histology was evaluated by hematoxylin-eosin and Masson's trichrome staining. The content of ATP, MPO, and the activity of mitochondrial respiratory chain complex Ⅳ were determined by ELISA. Western blot was performed to assess the expression of ATP5D and related signaling proteins, and the mediators of myocardial fibrosis.
Treatment with CP diminished myocardial infarct size, retained myocardium structure, attenuated myocardial fibrosis, and restored MBF. CP ameliorated energy metabolism disorder, attenuated TGFβ1 up-regulation and reversed its downstream gene expression, such as Smad6 and Smad7, and inhibited the increased expression of MCP-1, PR S19, MMP-2 and MMP-9.
CP effectively protects myocardial structure and function from ISR challenge, possibly by regulating energy metabolism via inactivation of RhoA/ROCK signaling pathway and inhibition of monocyte chemotaxis and TGF β1/Smads signaling pathway.
支架植入术已被越来越多地应用于治疗阻塞性冠状动脉疾病，尽管其效果显著，但常因支架内再狭窄（ISR）而困扰患者。
本研究旨在探讨复方中药强心丸（CP）在减轻 ISR 引起的心肌损伤和纤维化中的作用。
采用植入废弃可降解支架的方法建立小型猪 ISR 模型，通过定量冠状动脉造影（QCA）确认模型的建立。
ISR 后每日给予 CP 0.2 g/kg，共 30 天。支架植入后 30 天和 60 天，评估心肌梗死和心肌血流（MBF）。苏木精-伊红和 Masson 三色染色评估心肌组织学。通过 ELISA 测定 ATP、MPO 和线粒体呼吸链复合物Ⅳ活性。通过 Western blot 评估 ATP5D 及其相关信号蛋白和心肌纤维化介质的表达。
CP 治疗可减小心肌梗死面积，保留心肌结构，减轻心肌纤维化，恢复 MBF。CP 改善能量代谢障碍，减弱 TGFβ1 的上调并逆转其下游基因表达，如 Smad6 和 Smad7，并抑制 MCP-1、PR S19、MMP-2 和 MMP-9 的表达增加。
CP 可有效保护心肌结构和功能免受 ISR 挑战，可能通过抑制 RhoA/ROCK 信号通路和抑制单核细胞趋化和 TGFβ1/Smads 信号通路来调节能量代谢。
