NRG-1βはJNKシグナル伝達経路を介して、ラットの虚血再灌流誘発性傷害に対して神経保護効果を発揮する

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Neuroscience.2017 Oct;362:13-24. S0306-4522(17)30598-5. doi: 10.1016/j.neuroscience.2017.08.032.Epub 2017-08-23.

NRG-1βはJNKシグナル伝達経路を介して、ラットの虚血再灌流誘発性傷害に対して神経保護効果を発揮する

NRG-1β exerts neuroprotective effects against ischemia reperfusion-induced injury in rats through the JNK signaling pathway.

Yaqing Ji
Lei Teng
Rui Zhang
Jinping Sun
Yunliang Guo

PMID: 28843994 DOI: 10.1016/j.neuroscience.2017.08.032.

抄録

背景:

ニューレグリン-1β（NRG-1β）は、神経保護のための治療薬として開発される可能性を秘めています。本研究の目的は、中大脳動脈閉塞/再灌流モデル（MCAO/R）ラットを用いて、NRG-1βの脳組織への影響とそのシグナル伝達経路の可能性を解析することである。

BACKGROUND: Neuregulin-1β (NRG-1β) has great potential to be developed into therapeutics for neuroprotection. The aim of the current study was to analyze the effects and possible signaling pathway of NRG-1β on brain tissues in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R).

方法:

METHODS: In order to observe the protective effect of NRG-1β on MCAO/R, the neurological deficit and infarct volume were measured using a modified neurological severity score (mNSS) test and by triphenyl tetrazolium chloride (TTC) staining. In order to detect the antagonistic effect of NRG-1β on nerve cells and the blood-brain barrier (BBB), the morphology and structure of cortical brain tissues were observed by Evans Blue (EB) staining, hematoxylin-eosin (H&E) and Nissl staining, in situ cell death detection kit, and transmission electron microscopy (TEM). In order to investigate whether NRG-1β exhibited a significant neuroprotective effect via the JNK signaling pathway, the activity of JNK and the levels of phospho-MKK4, phospho-JNK, pan-JNK and phospho-c-Jun were tested using a JNK activity screening kit, immunofluorescent labeling, and western blot analysis, respectively.

結果:

NRG-1β投与群では、JNK活性の低下に伴い、phospho-JNK、phospho-MKK4、phospho-c-Junのタンパク質レベルが低下し、虚血誘発性アポトーシスが減少し、神経細胞の異常な形態学的構造が改善され、BBBの完全性が回復し、梗塞容積が減少した。同時に、神経機能も有意に回復した。

RESULTS: In the NRG-1β treatment group, accompanied with a decrease in JNK activity, the protein levels of phospho-JNK, phospho-MKK4 and phospho-c-Jun decreased, the ischemia-induced apoptosis decreased, the abnormal morphological structures of nerve cells were ameliorated, the integrity of the BBB was restored, and infarct volume was reduced. At the same time, neurological function was significantly recovered.

結論:

NRG-1βはMCAO/RラットにおいてJNKシグナル伝達経路を介して神経保護効果を発揮する。

CONCLUSION: NRG-1β exerts a neuroprotective effect through the JNK signaling pathway in MCAO/R rats.