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一种新型脑梗死栓塞模型及新型真菌三萜酚代谢物密粘褶菌三萜酚-7(SMTP-7)的评价。

A novel embolic model of cerebral infarction and evaluation of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite.

机构信息

Department of Pharmacology, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

出版信息

J Pharmacol Sci. 2010;114(1):41-9. doi: 10.1254/jphs.10131fp. Epub 2010 Aug 10.

Abstract

The aim of the present study was to establish a novel embolic model of cerebral infarction and to evaluate the effect of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite. Thrombotic occlusion was induced by transfer of acetic acid-induced embolus into the brain. The regional cerebral blood flow was measured by a laser Doppler flowmeter to check the ischemic condition. Infarction area was assessed by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological scores were determined by a modified version of the method described by Longa et al. Emboli were accumulated at the temporal or parietal region of the middle cerebral artery. Additionally, we found that this model showed decreased cerebral blood flow and increased infarction area and neurological scores. Treatment with tissue plasminogen activator (t-PA) reduced infarction area and the neurological scores in a dose-dependent manner; moreover, the decreased cerebral blood flow recovered. SMTP-7 also reduced these values. The therapeutic time window of SMTP-7 was longer than that of t-PA. These results indicate that this model may be useful for understanding the pathophysiological mechanisms of cerebral infarction and evaluating the effects of therapeutic agents. Additionally, SMTP-7 is a promising approach to extend the therapeutic time window. Therefore, this novel compound may represent a novel approach for the treatment of cerebral infarction.

摘要

本研究旨在建立一种新的脑梗死栓塞模型,并评估新型真菌三萜酚代谢物密粘褶菌三萜酚-7(SMTP-7)的作用。通过将乙酸诱导的栓子转移到大脑中诱导血栓闭塞。使用激光多普勒血流计测量局部脑血流以检查缺血情况。通过 2% 2,3,5-三苯基氯化四氮唑(TTC)染色评估梗死面积。通过改良的 Longa 等描述的方法确定神经评分。栓子积聚在大脑中动脉的颞部或顶叶区域。此外,我们发现该模型显示脑血流减少、梗死面积增加和神经评分升高。组织型纤溶酶原激活剂(t-PA)的治疗剂量依赖性地降低了梗死面积和神经评分;此外,降低的脑血流得到恢复。SMTP-7 也降低了这些值。SMTP-7 的治疗时间窗长于 t-PA。这些结果表明,该模型可能有助于理解脑梗死的病理生理机制,并评估治疗药物的效果。此外,SMTP-7 是延长治疗时间窗的有前途的方法。因此,这种新型化合物可能代表治疗脑梗死的新方法。

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