Ultrasound-Induced Destruction of Nitric Oxide-Loaded Microbubbles in the Treatment of Thrombus and Ischemia-Reperfusion Injury

doi:10.3389/fphar.2021.745693

科研成果详情

题名	Ultrasound-Induced Destruction of Nitric Oxide-Loaded Microbubbles in the Treatment of Thrombus and Ischemia-Reperfusion Injury
作者	Liang, Zenghui 1; Chen, Huafang2; Gong, Xuehao 3; Shi, Binbin 1; Lin, Lili 1; Tao, Fangyi 1; Wu, Qilong1; Fang, Mingling 1; Li, Hui 1; Lu, Cuitao4; Xu, Helin1,4; Zhao, Yingzheng1,4; Chen, Bin 1,3
发表日期	2022-01-04
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	nitric oxide thrombus ischemia-reperfusion injury ultrasound-targeted microbubbles destruction endothelial nitric oxide synthase
其他关键词	MYOCARDIAL-ISCHEMIA ; THERAPEUTIC ULTRASOUND ; TARGETED MICROBUBBLE ; IN-VIVO ; CAVITATION ; DELIVERY ; ENHANCEMENT ; MECHANISMS ; INHALATION ; FLOW
摘要	Objectives: Early recanalization of large vessels in thromboembolism, such as myocardial infarction and ischemic stroke, is associated with improved clinical outcomes. Nitric oxide (NO), a biological gas signaling molecule, has been proven to protect against ischemia-reperfusion injury (IRI). However, the underlying mechanisms remain to be explored. This study investigated whether NO could mitigate IRI and the role of NO during acoustic cavitation.Methods: In vivo, thrombi in the iliac artery of rats were induced by 5% FeCl3. NO-loaded microbubbles (NO-MBs) and ultrasound (US) were used to treat thrombi. B-mode and Doppler US and histological analyses were utilized to evaluate the thrombolysis effect in rats with thrombi. Immunohistochemistry, immunofluorescence, and western blotting were conducted to investigate the underlying mechanisms of NO during acoustic cavitation. In vitro, hypoxia was used to stimulate cells, and NO-MBs were employed to alleviate oxidative stress and apoptosis.Results: We developed NO-MBs that significantly improve the circulation time of NO in vivo, are visible, and effectively release therapeutic gas under US. US-targeted microbubble destruction (UTMD) and NO-loaded UTMD (NO + UTMD) caused a significant decrease in the thrombus area and an increase in the recanalization rates and blood flow velocities compared to the control and US groups. We discovered that UTMD induced NO generation through activation of endothelial NO synthase (eNOS) in vivo. More importantly, we also observed significantly increased NO content and eNOS expression in the NO + UTMD group compared to the UTMD group. NO + UTMD can mitigate oxidative stress and apoptosis in the hind limb muscle without influencing blood pressure or liver and kidney functions. In vitro, NO-MBs alleviated oxidative stress and apoptosis in cells pretreated with hypoxia.Conclusion: Based on these data, UTMD affects the vascular endothelium by activating eNOS, and NO exerts a protective effect against IRI.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81903551, 81803443]; Zhejiang Province Natural Science FoundationNatural Science Foundation of Zhejiang Province [LY19H180001]; Wenzhou Science and Technology Bureau [Y20180283]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1663-9812
EISSN	1663-9812
卷号	12 页码:745693
DOI	10.3389/fphar.2021.745693
页数	15
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000748030500001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35082664
PMC记录号	PMC8785684
SCOPUSEID	2-s2.0-85123421495
通讯作者地址	[Zhao, Yingzheng]Department of Ultrasonography,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China ; [Chen, Bin]Department of Ultrasonography,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6017
专题	第二临床医学院、附属第二医院、育英儿童医院_影像医学与核医学_超声科药学院（分析测试中心）附属第一医院_超声影像科附属第一医院_药物临床试验机构办公室
通讯作者	Zhao, Yingzheng; Chen, Bin
作者单位	1.Department of Ultrasonography,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.The Office of Drug Clinical Trial Institution,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Department of Ultrasound,First Affiliated Hospital of Shenzhen University,Second People's Hospital of Shenzhen,Shenzhen,China; 4.Department of Pharmaceutics,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Liang, Zenghui,Chen, Huafang,Gong, Xuehao,et al. Ultrasound-Induced Destruction of Nitric Oxide-Loaded Microbubbles in the Treatment of Thrombus and Ischemia-Reperfusion Injury[J]. FRONTIERS IN PHARMACOLOGY,2022,12:745693.
APA	Liang, Zenghui., Chen, Huafang., Gong, Xuehao., Shi, Binbin., Lin, Lili., ... & Chen, Bin. (2022). Ultrasound-Induced Destruction of Nitric Oxide-Loaded Microbubbles in the Treatment of Thrombus and Ischemia-Reperfusion Injury. FRONTIERS IN PHARMACOLOGY, 12, 745693.
MLA	Liang, Zenghui,et al."Ultrasound-Induced Destruction of Nitric Oxide-Loaded Microbubbles in the Treatment of Thrombus and Ischemia-Reperfusion Injury".FRONTIERS IN PHARMACOLOGY 12(2022):745693.