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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

P-EKKE Alleviates Myocardial Infarction (MI) in MI Rats by Inhibiting Hedgehog Signaling Pathway-mediated Inflammation and Inhibiting α-actin Mediated Myocardial Fibrosis

Author(s): Guixian Song, Zhongbao Ruan, Ruzhu Wang, Yin Ren, Li Zhu, Yahui Shen* and Bin Wang*

Volume 21, Issue 7, 2024

Published on: 27 March, 2023

Page: [1164 - 1171] Pages: 8

DOI: 10.2174/1570180820666230217094512

Price: $65

Abstract

Background: Myocardial infarction (MI) is an ischemic heart disorder that causes apoptosis or necrosis of myocardial cells.

Objective: The study aimed to evaluate the effect of P-EKKE on myocardial infarction and explore the associated mechanisms in MI rats.

Methods: The MI in rats was established by ligating the left coronary artery of rats; the rats were divided into the MI group (without treatment) and the P-EKKE group (treated with P-EKKE). Normal rats were assigned to the NC group (without treatment) and the sham group (under LAD without ligation). Cardiac function was evaluated using echocardiography. The MI area was measured with TTC staining. Histological analysis was performed to evaluate inflammation (HE staining) and myocardial fibrosis (Masson and immunofluorescence staining). RT-PCR and Western blotting were used to determine Gli-1/SHH expression in myocardial tissues.

Results: P-EKKE clearly improved the cardiac function of MI rats. The area of myocardial infarction in MI rats undergoing P-EKKE treatment (P-EKKE group) was found to be predominantly decreased compared to MI rats without treatment (p < 0.05). P-EKKE treatment clearly inhibited apoptosis and increased H3S10ph expression in the area of myocardial infarction of MI rats compared to MI rats without treatment (p < 0.05). P-EKKE treatment significantly alleviated inflammation and decreased myocardial fibrosis in the area of myocardial infarction in MI rats compared to MI rats without treatment (p < 0.05). P-EKKE significantly increased the expression of Gil-1 and SHH in myocardial infarction of MI rats compared to MI rats without treatment (p < 0.05).

Conclusion: P-EKKE inhibited myocardial infarction and played an anti-inflammatory and myocardial protective role in MI rats. P-EKKE inhibited myocardial inflammation by activating the hedgehog signaling pathway and inhibited myocardial fibrosis by decreasing α-actin expression.

Keywords: Myocardial infarction, P-EKKE, cardiac function, myocardial cells, inflammation, hedgehog signaling pathway.

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