Evaluation of the effects of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model
Evaluation of the effects of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model
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DOI：
10.1016/j.ejphar.2017.10.055
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发表时间：
2018-01-05
影响因子：
5
通讯作者：
Nobe, Koji
中科院分区：
文献类型：
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作者：
Shibata, Keita;Hashimoto, Terumasa;Nobe, Koji
我们以前报道过，小孢穗柄霉三异戊二烯基苯酚-7（SMTP-7）显示出潜在的溶栓、抗炎和抗氧化作用，这是其优异的药理活性的原因，例如具有比组织纤溶酶原激活剂（t-PA）更宽的治疗时间窗和显著的抗出血保护作用。本研究的目的是评价和比较一系列新的SMTP在乙酸诱导的栓塞性脑梗死小鼠模型中的作用。通过诱导乙酸诱导的血栓从右颈总动脉转移到脑中，在小鼠中产生血栓闭塞。通过减少梗死面积、神经功能评分和水肿的效果来评价SMTP。此外，纤溶酶的形成，抗炎和抗氧化活性进行了评估，通过纤维蛋白酶谱，测量促炎基因表达，硫代巴比妥酸反应物质（TBARS）测定，分别。用SMTP-22或SMTP-43（10 mg/kg）（其具有与SMTP-7相似的纤溶酶形成、抗炎和抗氧化活性）治疗导致梗死面积、神经评分和水肿减少。所有这三种活性的共存对于栓塞性梗死的治疗似乎是重要的，因为SMTP-6、SMTP-25和SMTP-44 D（10 mg/kg），其各自缺失三种功能中的至少一种，不那么有效。因此，这些结果表明，SMTP-22和SMTP-43具有作为治疗栓塞性脑梗死的药物化合物的潜力。
We reported previously that Stachybotrys microspora triprenyl phenol-7 (SMTP-7) showed potential thrombolytic, anti-inflammatory and anti-oxidant effects that account for its excellent pharmacological activity such as having a wider therapeutic time window than tissue plasminogen activator (t-PA) and a significant protection against hemorrhage. The aim of the present study was to evaluate and compare the effect of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model. Thrombotic occlusion was produced in mice by inducing the transfer of acetic acid-induced thrombi from the right common carotid artery into the brain. SMTPs were evaluated by their effect on reducing infarct area, neurological score and edema. Furthermore, plasmin formation, anti-inflammatory and anti-oxidant activities were assessed by fibrin zymography, measuring pro-inflammatory gene expression, and thiobarbituric acid reactive substances (TBARS) assay, respectively. Treatment with either SMTP-22 or SMTP-43 (10 mg/kg), which have similar plasmin formation, anti-inflammatory and anti-oxidant activities to SMTP-7, resulted in reduced infarct area, neurological score and edema. Coexistence of all these three activities appears to be important for the treatment of embolic infarction because SMTP-6, SMTP-25, and SMTP-44D (10 mg/kg), which are each missing at least one of the three functions, were not as effective. Therefore, these results indicate that SMTP-22 and SMTP-43 have potential as medicinal compounds for the treatment of embolic cerebral infarction.