硝基阿司匹林（NCX4016）可减轻大鼠局灶性脑缺血所致的脑损伤。

Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat.

作者信息

Fredduzzi S, Mariucci G, Tantucci M, Del Soldato P, Ambrosini M V

机构信息

Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Sezione di Biologia Sperimentale, Via del Giochetto, 06124, Perugia, Italy.

出版信息

Neurosci Lett. 2001 Apr 20;302(2-3):121-4. doi: 10.1016/s0304-3940(01)01672-x.

DOI:10.1016/s0304-3940(01)01672-x

PMID:11290402

Abstract

The potential neuroprotective effects of the novel nitro-derivate of aspirin (NCX4016) on permanent focal cerebral ischemia in spontaneously hypertensive rats (SHRs) was investigated. Reference compounds were acetylsalicilic acid (ASA) and FK506 (tacrolimus). Ten minutes after surgery, SHRs were randomly divided into four groups of ten, pharmacologically treated and sacrificed 24 h after treatment. Brains were removed and processed to measure infarct volume, 70 kDa heat shock protein (hsp70), glial fibrillary acidic protein (GFAP) and vimentin (Vim) immunoreactivity (IR), and apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. NCX-4016 significantly reduced total infarct volume compared to ASA (-20%, P < 0.05), FK506 (-18%, P < 0.05) and vehicle treatment (-20%, P < 0.05). Experimental groups did not differ in hsp70-IR and GFAP-IR. Conversely, hyperplastic astrocytes, measured by Vim-IR, were significantly lower in NCX-4016 than in the vehicle group (-36%, P<0.01). TUNEL assay indicated a significantly lower degree of apoptosis in NCX-4016 group than vehicle in both the homolateral (-27%, P < 0.01) and contralateral hemisphere (-29%, P < 0.05). These findings indicate that NO release associated with aspirin confers neuroprotective effects against ischemic injury.

摘要

研究了新型阿司匹林硝基衍生物（NCX4016）对自发性高血压大鼠（SHR）永久性局灶性脑缺血的潜在神经保护作用。对照化合物为乙酰水杨酸（ASA）和FK506（他克莫司）。手术10分钟后，将SHR随机分为四组，每组10只，进行药物治疗，并在治疗后24小时处死。取出大脑并进行处理，以测量梗死体积、70 kDa热休克蛋白（hsp70）、胶质纤维酸性蛋白（GFAP）和波形蛋白（Vim）免疫反应性（IR），并使用末端脱氧核苷酸转移酶（TdT）介导的dUTP-地高辛配基缺口末端标记（TUNEL）法检测细胞凋亡。与ASA（-20%，P<0.05）、FK506（-18%，P<0.05）和溶剂对照组（-20%，P<0.05）相比，NCX-4016显著降低了总梗死体积。实验组在hsp70-IR和GFAP-IR方面没有差异。相反，通过Vim-IR测量，NCX-4016组的增生性星形胶质细胞明显低于溶剂对照组（-36%，P<0.01）。TUNEL检测表明，NCX-4016组同侧（-27%，P<0.01）和对侧半球（-29%，P<0.05）的细胞凋亡程度均明显低于溶剂对照组。这些发现表明，与阿司匹林相关的一氧化氮释放赋予了对缺血性损伤的神经保护作用。