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

被引:0
作者
Song, Guixian [1 ]
Ruan, Zhongbao [1 ]
Wang, Ruzhu [1 ]
Ren, Yin [1 ]
Zhu, Li [1 ]
Shen, Yahui [2 ]
Wang, Bin [1 ]
机构
[1] Nanjing Med Univ, Affiliated Taizhou Peoples Hosp, Taizhou Sch Clin Med, Dept Cardiol, Taizhou 225300, Peoples R China
[2] Nanjing Med Univ, Affiliated Taizhou Peoples Hosp, Taizhou Sch Clin Med, Dept Resp & Crit Care Med, Taizhou 225300, Peoples R China
基金
中国国家自然科学基金;
关键词
Myocardial infarction; P-EKKE; cardiac function; myocardial cells; inflammation; hedgehog signaling pathway; HEART-FAILURE; ACTIVATION;
D O I
10.2174/1570180820666230217094512
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 alpha-actin expression.
引用
收藏
页码:1164 / 1171
页数:8
相关论文
共 27 条
[1]  
Branton A., 2019, J. Cardiol, V3
[2]   The mechanisms of Hedgehog signalling and its roles in development and disease [J].
Briscoe, James ;
Therond, Pascal P. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (07) :416-429
[3]   Gi proteins mediate activation of the canonical hedgehog pathway in the myocardium [J].
Carbe, Christian J. ;
Cheng, Lan ;
Addya, Sankar ;
Gold, Jessica I. ;
Gao, Erhe ;
Koch, Walter J. ;
Riobo, Natalia A. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2014, 307 (01) :H66-H72
[4]   Targeting inflammatory pathways in myocardial infarction [J].
Christia, Panagiota ;
Frangogiannis, Nikolaos G. .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2013, 43 (09) :986-995
[5]   Myofibroblasts: Trust your heart and let fate decide [J].
Davis, Jennifer ;
Molkentin, Jeffery D. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2014, 70 :9-18
[6]   Altering Sphingolipid Metabolism Attenuates Cell Death and Inflammatory Response After Myocardial Infarction [J].
Hadas, Yoav ;
Vincek, Adam S. ;
Youssef, Elias ;
Zak, Magdalena M. ;
Chepurko, Elena ;
Sultana, Nishat ;
Sharkar, Mohammad Tofael Kabir ;
Guo, Ningning ;
Komargodski, Rinat ;
Kurian, Ann Anu ;
Kaur, Keerat ;
Magadum, Ajit ;
Fargnoli, Anthony ;
Katz, Michael G. ;
Hossain, Nadia ;
Kenigsberg, Ephraim ;
Dubois, Nicole C. ;
Schadt, Eric ;
Hajjar, Roger ;
Eliyahu, Efrat ;
Zangi, Lior .
CIRCULATION, 2020, 141 (11) :916-930
[7]  
Han Y., 2020, Pract J Cardiac Cerebr Pneum Vasc Dis, V28, P109
[8]   Therapeutic approaches for cardiac regeneration and repair [J].
Hashimoto, Hisayuki ;
Olson, Eric N. ;
Bassel-Duby, Rhonda .
NATURE REVIEWS CARDIOLOGY, 2018, 15 (10) :585-600
[9]   Hedgehog signaling in animal development: paradigms and principles [J].
Ingham, PW ;
McMahon, AP .
GENES & DEVELOPMENT, 2001, 15 (23) :3059-3087
[10]   Progress and Challenge of Cardiac Regeneration to Treat Heart Failure [J].
Isomi, Mari ;
Sadahiro, Taketaro ;
Ieda, Masaki .
JOURNAL OF CARDIOLOGY, 2019, 73 (1-2) :97-101