Xueshuantong injection alleviates cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion rats by suppressing inflammation via JNK mediated JAK2/STAT3 and NF-κB signaling pathways

三七 微循环 医学 血脑屏障 炎症 药理学 病理 内科学 中枢神经系统 替代医学
作者
Gaorui Wang,Ziyu Chen,Yingying Song,Hui Wu,Ming Chen,Shusheng Lai,Xiaojun Wu
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:298: 115592-115592 被引量:12
标识
DOI:10.1016/j.jep.2022.115592
摘要

In the long history of traditional Chinese medicine, Panax notoginseng has been used as a key herb for the treatment of blood diseases. Brain microvessels support adequate blood circulation to maintain normal physiological function, therefore, brain microcirculation disorder is an important therapeutic target for various brain diseases. However, the role of Xueshuantong (XST) injection composed of saponins from P. Notoginseng (PNS) in the amelioration of cerebral microcirculation disorder is unclear.Cerebral microcirculation disorder and inflammation play a vital role in stroke. Capillary endothelial cells and adjacent tight junctions are fundamental to the structure and function of cerebrovascule. XST injection has been used clinically in the treatment of stroke, but no studies have reported its indication in cerebral microcirculation disorder. This study is to explore the action and mechanism of XST injection in the alleviation of cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion (MCAO/R) rats.MCAO/R rats and LPS-induced bEnd.3 cells were employed for the investigation of effect and mechanism of XST injection. Brain damages were evaluated by neurobehavioral assessment, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining (H&E), and Nissl staining. Morphology and density changes of cerebral microvessels were monitored by immunohistochemistry. Cell permeability was detected by measurement of trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. The mRNA and protein expressions of inflammatory cytokines, tight junction proteins, adhesion molecules, Janus kinase 2 (JAK2), signal transducer and activator of transcription-3 (STAT3), inhibitor of NF-κB (IκB), nuclear factor-κB (NF-κB) and c-jun N-terminal kinase (JNK) in brain microvessels and lipopolysaccharide (LPS)-induced bEnd.3 cells were measured by real-time PCR and Western blot, respectively.XST injection at 48 mg/kg significantly improved the neurological damage, inflammatory infiltration, and microvessel morphology, and increased microvessel density in brain of MCAO/R rats. The endothelial permeability was significantly mitigated by XST injection in LPS-induced bEnd.3 cells. Meanwhile, the tight junction proteins such as zona occludens 1 (ZO-1) and occludin were elevated remarkably in brain microvessel of MCAO/R rats and LPS-induced bEnd.3 cells. Moreover, the expression of inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), cycloocygenases 2 (COX-2), vascular cellular adhesion molecule-1 (VCAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 were inhibited by XST injection. In addition, XST injection suppressed the phosphorylation of JAK2, STAT3, IκB, NF-κB and JNK, which could be abolished by anisomycin, the JNK agonist.XST injection improved cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
SCI驳回了胡子木应助
刚刚
刘十三完成签到,获得积分10
刚刚
小马甲应助稳重向南采纳,获得10
刚刚
xrf完成签到,获得积分10
2秒前
江枫完成签到 ,获得积分10
3秒前
3秒前
细腻的宫二完成签到,获得积分10
3秒前
幽默泥猴桃完成签到,获得积分10
4秒前
wlqc完成签到,获得积分10
5秒前
5秒前
yjzzz完成签到,获得积分10
5秒前
xiaolingc完成签到,获得积分10
5秒前
longjie完成签到,获得积分10
7秒前
144完成签到 ,获得积分10
8秒前
11111发布了新的文献求助10
8秒前
两院候选人应助家鹭洋采纳,获得10
8秒前
lsq发布了新的文献求助10
9秒前
白衣修身完成签到,获得积分10
9秒前
张大忽悠完成签到,获得积分10
9秒前
9秒前
hello完成签到 ,获得积分10
10秒前
老邱完成签到,获得积分10
10秒前
哒哒完成签到,获得积分10
11秒前
高贵绿真完成签到 ,获得积分10
11秒前
道明嗣完成签到 ,获得积分10
11秒前
张小陈完成签到 ,获得积分10
12秒前
吉羿发布了新的文献求助10
12秒前
12秒前
wanwei完成签到,获得积分10
13秒前
科研通AI2S应助SciEngineerX采纳,获得10
13秒前
14秒前
bazinga应助阮煜城采纳,获得10
14秒前
典雅威完成签到,获得积分10
14秒前
14秒前
张大忽悠发布了新的文献求助10
14秒前
路瑶瑶完成签到,获得积分10
14秒前
maorongfu456完成签到,获得积分10
15秒前
orange完成签到 ,获得积分10
15秒前
ztt27999完成签到,获得积分10
15秒前
16秒前
高分求助中
Licensing Deals in Pharmaceuticals 2019-2024 3000
Cognitive Paradigms in Knowledge Organisation 2000
Effect of reactor temperature on FCC yield 2000
Introduction to Spectroscopic Ellipsometry of Thin Film Materials Instrumentation, Data Analysis, and Applications 1200
How Maoism Was Made: Reconstructing China, 1949-1965 800
Medical technology industry in China 600
Shining Light on the Dark Side of Personality 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3311457
求助须知:如何正确求助?哪些是违规求助? 2944239
关于积分的说明 8518079
捐赠科研通 2619580
什么是DOI,文献DOI怎么找? 1432472
科研通“疑难数据库(出版商)”最低求助积分说明 664671
邀请新用户注册赠送积分活动 649869