资源类型：
期刊
WOS体系：
Article
Pubmed体系：
Journal Article;Research Support, Non-U.S. Gov't
收录情况：
◇ SCIE
文章类型：
论著
机构：
[a]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
神经科系统
神经外科
首都医科大学宣武医院
[b]Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
[c]Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
ISSN：
0014-4886
关键词：
LJ529 Adenosine A3 receptor Mast cells Inflammation Subarachnoid hemorrhage
摘要：
Background and purpose: Mast cells (MCs) has been recognized as an effector of inflammation or a trigger of inflammatory factors during stroke. LJ529 was reported to attenuate inflammation through a Gi protein-coupled Adenosine A3 receptor (A3R) after ischemia. Here, we aim to study the protective effect and its mechanism of LJ529 in subarachnoid hemorrhage (SAH) rat model for mast cell-related inflammation. Methods: 155 Sprague–Dawley adult male rats were used in experiments. Endovascular perforation was used for SAH model. Intraperitoneal LJ529 was performed 1 h after SAH. Neurological scores were measured 24 h after SAH. Rotarod and morris water maze tests were evaluated for 21 days after SAH. Mast cell degranulation was assessed with Toluidine blue staining and Chymase/Typtase protein expressions. Mast cell-related inflammation was evaluated using IL-6, TNF-α and MCP-1 protein expressions. MRS1523, inhibitor of GPR18 and ε-V1-2, inhibitor of PKCε were respectively given intraperitoneally (i.p.) 1 h and 30 min before SAH for mechanism studies. Pathway related proteins were investigated with western blot and immunofluorescence staining. Results: Expression of A3R, PKCε increased after SAH. LJ529 treatment attenuated mast cell degranulation and inflammation. Meanwhile, both short-term and long-term neurological functions were improved after LJ529 treatment. Administration of LJ529 resulted in increased expressions of A3R, PKCε, ALDH2 proteins and decreased expressions of Chymase, Typtase, IL-6, TNF-α and MCP-1 proteins. MRS1523 abolished the treatment effects of LJ529 on neurobehavior and protein levels. ε-V1-2 also reversed the outcomes of LJ529 administration through reduction in protein expressions downstream of PKCε. Conclusions: LJ529 attenuated mast cell-related inflammation through inhibiting degranulation via A3R-PKCε-ALDH2 pathway after SAH. LJ529 may serve as a potential treatment strategy to relieve post-SAH brain injury. © 2021
基金：
Beijing Postdoctoral Science Foundation to Dr. TY Zhang [grants No. 2020-ZZ-020]; China Postdoctoral Science Foundation to Dr. TY Zhang [grants No. 2019TQ0216 and 2019M660716]. The National Natural Science Foundation of China to Dr. TY Zhang [grant No. 82001324].
被引次数：
6
WOS：
WOS:000648654800006
PubmedID：
33713658
中科院(CAS)分区：
出版当年[2020]版：
大类
|
2 区
医学
小类
|
2 区
神经科学
最新[2023]版：
大类
|
2 区
医学
小类
|
2 区
神经科学
JCR分区：
出版当年[2019]版：
Q1
NEUROSCIENCES
最新[2023]版：
Q1
NEUROSCIENCES
影响因子：
4.6
最新[2023版]
4.8
最新五年平均
4.691
出版当年[2019版]
4.767
出版当年五年平均
4.562
出版前一年[2018版]
5.33
出版后一年[2020版]
第一作者：
Zhang, T
第一作者机构：
[a]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
通讯作者：
Zhang, H
通讯机构：
[*1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing 100053, China.
推荐引用方式(GB/T 7714)：
Zhang T,Huang L,Peng J,et al.LJ529 attenuates mast cell-related inflammation via A3R-PKCε-ALDH2 pathway after subarachnoid hemorrhage in rats[J].EXPERIMENTAL NEUROLOGY.2021,340:doi:10.1016/j.expneurol.2021.113686.
APA：
Zhang, T,Huang, L,Peng, J,Zhang, J.H&Zhang, H.(2021).LJ529 attenuates mast cell-related inflammation via A3R-PKCε-ALDH2 pathway after subarachnoid hemorrhage in rats.EXPERIMENTAL NEUROLOGY,340,
MLA：
Zhang, T,et al."LJ529 attenuates mast cell-related inflammation via A3R-PKCε-ALDH2 pathway after subarachnoid hemorrhage in rats".EXPERIMENTAL NEUROLOGY 340.(2021)
