Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion in...

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Main Authors: Ying Sun, Boyang Jiao, Yizhou Liu, Ran Wang, Qiong Deng, David N. Criddle, Yulin Ouyang, Wei Wang, Xuegong Xu, Chun Li
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Traditional Chinese Medical Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S2095754824001054
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author Ying Sun
Boyang Jiao
Yizhou Liu
Ran Wang
Qiong Deng
David N. Criddle
Yulin Ouyang
Wei Wang
Xuegong Xu
Chun Li
author_facet Ying Sun
Boyang Jiao
Yizhou Liu
Ran Wang
Qiong Deng
David N. Criddle
Yulin Ouyang
Wei Wang
Xuegong Xu
Chun Li
author_sort Ying Sun
collection DOAJ
description Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion: STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
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spelling doaj-art-3582facf5b894228b63f1cd952aede602025-01-25T04:11:14ZengElsevierJournal of Traditional Chinese Medical Sciences2095-75482025-01-011213143Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathwayYing Sun0Boyang Jiao1Yizhou Liu2Ran Wang3Qiong Deng4David N. Criddle5Yulin Ouyang6Wei Wang7Xuegong Xu8Chun Li9School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaModern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaDepartment of Cellular &amp; Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, United KingdomShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Ministry of Education, Beijing 102488, ChinaDepartment of Geriatrics, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou 450007, China; Institute of Geriatric Diseases, Henan Academy of Traditional Chinese Medicine, Zhengzhou 450046, China; Corresponding authors.Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Ministry of Education, Beijing 102488, China; Corresponding authors.Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion: STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.http://www.sciencedirect.com/science/article/pii/S2095754824001054Coronary artery microvascular diseaseShexiang Tongxin dropping pillsIschemia-reperfusion injuryMicrovascular barrier functionS1PR2/RhoA/ROCK pathway
spellingShingle Ying Sun
Boyang Jiao
Yizhou Liu
Ran Wang
Qiong Deng
David N. Criddle
Yulin Ouyang
Wei Wang
Xuegong Xu
Chun Li
Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
Journal of Traditional Chinese Medical Sciences
Coronary artery microvascular disease
Shexiang Tongxin dropping pills
Ischemia-reperfusion injury
Microvascular barrier function
S1PR2/RhoA/ROCK pathway
title Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
title_full Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
title_fullStr Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
title_full_unstemmed Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
title_short Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
title_sort shexiang tongxin dropping pills ameliorate myocardial ischemia reperfusion injury progression via the s1pr2 rhoa rock pathway
topic Coronary artery microvascular disease
Shexiang Tongxin dropping pills
Ischemia-reperfusion injury
Microvascular barrier function
S1PR2/RhoA/ROCK pathway
url http://www.sciencedirect.com/science/article/pii/S2095754824001054
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