当前位置： SCI文献检索 > NEUROCHEMICAL RESEARCH期刊下所有文献 > Dendrobium Alkaloids Promote Neural Function After Cerebral Ischemia-Reperfusion Injury Through Inhibiting Pyroptosis Induced Neuronal Death in both In Vivo and In Vitro Models.

Dendrobium Alkaloids Promote Neural Function After Cerebral Ischemia-Reperfusion Injury Through Inhibiting Pyroptosis Induced Neuronal Death in both In Vivo and In Vitro Models.

Abstract：

:Pyroptosis is a newly identified lytic form of programmed cell death which is characterized by plasma membrane blebbing and rupture. Pyroptosis occurs in cerebral ischemia injury, and contributes to the activation and secretion of the inflammatory cytokines interleukin (IL)-1β, IL-18, and IL-6. Previous reports have found that Dendrobium alkaloids (DNLA) can exert neuroprotective effects against oxygen-glucose deprivation/reperfusion (OGD/R) damage in vitro, but the mechanisms underlying these effects remain elusive. In this study, we investigated whether DNLA exerted therapeutic benefits against cerebral ischemia-reperfusion (CIR) damage via ameliorating pyroptosis and inflammation. OGD/R damage was induced in HT22 cells pretreated with DNLA (0.03, 0.3, or 3 mg/ml, 24 h prior to OGD/R), MCC950 (10 ng/ml, 1 h prior), and VX765 (10 ng/ml, 1 h prior). Neuronal apoptosis, necrosis, pyroptosis, and pathological changes were analyzed 24 h following OGD/R. Further to this, male C57/BL mice pretreated with different concentrations of DNLA (0.5 or 5 mg/kg, ip.) for 24 h and VX765 (50 mg/kg, ip., 1 h before CIR) underwent transient middle cerebral artery occlusion and reperfusion. We found that DNLA pretreatment resulted in a lower neurologic deficit score, a reduced infarct volume, fewer pyroptotic cells, and reduced levels of inflammatory factors 24 h after CIR. Furthermore, DNLA administration also reduced the levels of the pyroptosis-associated proteins Caspase-1 and gasdermin-D, particularly in the hippocampal CA1 region. Similar decreases were observed in the levels of the inflammatory factors IL-1β, IL-6, and IL-18. OGD/R-associated ultrastructural damage was seen to improve following DNLA administration, likely due to the regulation of the tight junction protein Pannexin-1 by DNLA. Overall, these findings demonstrate that DNLA can protect against CIR damage through inhibiting pyroptosis-induced neuronal death, providing new therapeutic insights for CIR injury.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Liu D,Dong Z,Xiang F,Liu H,Wang Y,Wang Q,Rao J

doi

10.1007/s11064-019-02935-w

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

437-454

issue

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-019-02935-w

journal_volume

pub_type

杂志文章

在线工具

Dendrobium Alkaloids Promote Neural Function After Cerebral Ischemia-Reperfusion Injury Through Inhibiting Pyroptosis Induced Neuronal Death in both In Vivo and In Vitro Models.