Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice

doi:10.1016/j.intimp.2019.106180

科研成果详情

题名	Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice
作者	Cheng, Yijun 1; Chen, Bin 1; Xie, Wanqun 2; Chen, Zhenghong 1; Yang, Guoyuan 3,4; Cai, Yu 5; Shang, Hanbing 1; Zhao, Weiguo 1
发表日期	2020-02
发表期刊	INTERNATIONAL IMMUNOPHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Intracerebral hemorrhage Secondary brain injury Ghrelin Nrf2 NLRP3 inflammasome
其他关键词	OXIDATIVE STRESS ; SUBARACHNOID HEMORRHAGE ; TIME-COURSE ; CELL-DEATH ; NEUROPROTECTION ; PROTECTS ; MECHANISMS ; EXPRESSION ; MELATONIN ; ISCHEMIA
摘要	Ghrelin, a brain-gut peptide, has been proven to exert neuroprotection in different kinds of neurological diseases; however, its role and the potential molecular mechanisms in secondary brain injury (SBI) after intracerebral hemorrhage (ICH) are still unknown. In this study, we investigate whether treatment with ghrelin may attenuate SBI in a murine ICH model, and if so, whether the neuroprotective effects are due to the inhibition of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and promotion of nuclear factor-E2-related factor 2 (Nrf2)/antioxidative response element (ARE) signaling pathway. Stereotactically intrastriatal infusion of autologous blood was performed to mimic ICH. Ghrelin was given intraperitoneally immediately following ICH and again 1 h later. Results showed that ghrelin attenuated neuro-behavioral deficits, brain edema, hematoma volume, and perihematomal cell death post-ICH. Ghrelin inhibited the NLRP3 inflammasome activation and subsequently suppressed the neuroinflammatory response as evidenced by reduced microglia activation, neutrophil infiltration, and pro-inflammatory mediators release after ICH. Additionally, ghrelin alleviated ICH-induced oxidative stress according to the chemiluminescence of luminol and lucigenin, malondialdehyde (MDA) content, and total superoxide dismutase (SOD) activity assays. These changes were accompanied by upregulation of Nrf2 expression, Nrf2 nuclear accumulation, and enhanced Nrf2 DNA binding activity, as well as by increased expressions of Nrf2 downstream target antioxidative genes, including NAD(P)H quinine oxidoreductase-1 (NQO1), glutathione cysteine ligase regulatory subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM). Together, our data suggested that ghrelin protected against ICH-induced SBI by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway.
资助项目	Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [16ZR14212000]; SJTU Medicine-Engineering Translational Medicine Research Fund [ZH2018QNA50]; Ruijin Youth NSFC Cultivation Fund [2019QNPY01053]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	1567-5769
EISSN	1878-1705
卷号	79 页码:106180
DOI	10.1016/j.intimp.2019.106180
页数	13
WOS类目	Immunology ; Pharmacology & Pharmacy
WOS研究方向	Immunology ; Pharmacology & Pharmacy
WOS记录号	WOS:000514753800035
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	31926478
Scopus记录号	2-s2.0-85077442787
通讯作者地址	[Shang, Hanbing]Department of Neurosurgery,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China
scopus学科分类	Immunology and Allergy;Immunology;Pharmacology
引用统计	被引频次：18[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/18555
专题	附属第一医院_神经外科
通讯作者	Shang, Hanbing
作者单位	1.Department of Neurosurgery,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 2.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Neuroscience and Neuroengineering Research Center,Med-X Research Institute,Shanghai Jiao Tong University,Shanghai,China; 4.Department of Neurology,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 5.Department of Neurosurgery,North Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China
推荐引用方式 GB/T 7714	Cheng, Yijun,Chen, Bin,Xie, Wanqun,et al. Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2020,79:106180.
APA	Cheng, Yijun., Chen, Bin., Xie, Wanqun., Chen, Zhenghong., Yang, Guoyuan., ... & Zhao, Weiguo. (2020). Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice. INTERNATIONAL IMMUNOPHARMACOLOGY, 79, 106180.
MLA	Cheng, Yijun,et al."Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice".INTERNATIONAL IMMUNOPHARMACOLOGY 79(2020):106180.