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脑缺血后核结合蛋白-2通过调节Bcl-2/Bax比值及降低胶质纤维酸性蛋白表达发挥保护作用。

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.

作者信息

Erfani Sohaila, Moghimi Ali, Aboutaleb Nahid, Khaksari Mehdi

机构信息

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Department of Physiology, Faculty of Medicine, Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Basic Clin Neurosci. 2019 Sep-Oct;10(5):451-459. doi: 10.32598/bcn.10.5.451. Epub 2019 Sep 1.

Abstract

INTRODUCTION

Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemiareperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia.

METHODS

The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 μg/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining.

RESULTS

NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P<0.05). Also, NUCB2 increased Bcl-2 protein level (P<0.05). NUCB2 exerted protective effects against ischemic injury by the inhibition of astrocytes activation as an inflammatory response and decreased neuronal cell apoptosis.

CONCLUSION

The present study provides the possible neuroprotective view of nesfatin-1 in the treatment of ischemia injury model in rat hippocampus.

摘要

引言

核结合蛋白2(NUCB2)或nesfatin-1是一种新发现的厌食性肽,具有抗氧化、抗炎和抗凋亡特性。脑缺血再灌注会导致不可逆损伤,尤其是在海马区。然而,NUCB2在脑缺血中的治疗作用尚未得到充分研究。本研究首次设计旨在探讨在短暂性全脑缺血实验模型中,NUCB2/Nesfatin-1对海马CA1区凋亡相关蛋白表达和反应性星形胶质细胞增生水平的保护作用。

方法

将雄性Wistar大鼠随机分为4组(假手术组、NUCB2组、缺血再灌注组和缺血再灌注+NUCB2组)(n = 7)。通过结扎双侧颈总动脉20分钟制备脑缺血模型。在再灌注期开始时腹腔注射Nesfatin-1(20μg/kg)和生理盐水(作为溶剂)。通过免疫荧光和免疫组织化学染色评估蛋白表达水平。

结果

缺血后,NUCB2显著降低了CA1区的Bax和GFAP蛋白水平(P<0.05)。此外,NUCB2增加了Bcl-2蛋白水平(P<0.05)。NUCB2通过抑制作为炎症反应的星形胶质细胞活化和减少神经元细胞凋亡,对缺血性损伤发挥保护作用。

结论

本研究为nesfatin-1在大鼠海马缺血损伤模型治疗中的可能神经保护作用提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/702f/7149952/bdcb0f805999/BCN-10-451-g001.jpg

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