Huang Yong, Ohta Yasuyuki, Shang Jingwei, Li Xianghong, Liu Xia, Shi Xiaowen, Feng Tian, Yamashita Toru, Sato Kota, Takemoto Mami, Hishikawa Nozomi, Suzuki Eriko, Hasumi Keiji, Abe Koji
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kitaku, Okayama, Japan.
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Tokyo, Japan.
J Stroke Cerebrovasc Dis. 2018 Dec;27(12):3521-3528. doi: 10.1016/j.jstrokecerebrovasdis.2018.08.018. Epub 2018 Sep 7.
Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice.
After 60 minutes tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains.
SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect.
The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.
微小孢梗孢三萜烯酚-7(SMTP-7)具有溶栓和抗炎作用,但其对脑缺血的神经保护作用仍不清楚。本研究使用短暂性大脑中动脉闭塞(tMCAO)小鼠评估了SMTP-7的抗氧化和神经血管单元(NVU)保护作用。
在tMCAO 60分钟后,于再灌注前通过锁骨下静脉静脉注射0.9%氯化钠、组织型纤溶酶原激活剂(tPA)、SMTP-7或tPA + SMTP-7,并在再灌注后24小时对这些小鼠进行检查。我们对大脑中的出血情况和抗氧化标志物的表达变化进行了组织学评估。
SMTP-7治疗显示出与tPA相似的抗血栓作用,但显著降低了出血体积以及4-HNE、3-NT和8-OHdG阳性细胞的数量,同时改善了缺血脑中IV型胶原的减少。然而,tPA + SMTP-7治疗并未降低出血体积,也未显示出NVU保护作用。
本研究表明,与单独使用tPA或tPA + SMTP-7不同,SMTP-7通过抗氧化和NVU保护作用为缺血性中风提供了治疗益处。