海带岩藻聚糖硫酸酯对栓塞性脑缺血损伤的保护及作用机制的研究  

Protective activity of fucoidan from Laminaria japonica on the thromboembolic cerebral ischemia injury and its possible mechanism

作　　者：王展 郭峰君[2] 史姣霞 于彤[2] 赵雪[2] 孙锋 WANG Zhan;GUO Feng-jun;SHI Jiao-xia;YU Tong;ZHAO Xue;SUN Feng(Qingdao Center Medical group, Qingdao 266042, China;College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China)

机构地区：[1]青岛市中心医院,山东青岛266042 [2]中国海洋大学食品科学与工程学院,山东青岛266003

出　　处：《中国海洋药物》2018年第1期55-61,共7页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(31371759);国家自然科学基金委-山东省海洋科学研究联合基金(U1406402);海洋公益性行业科研专项经费项目(201505022)资助

摘　　要：目的对不同分子量海带岩藻聚糖硫酸酯对大鼠栓塞性脑缺血损伤的保护活性及其作用机制进行研究比较。方法以海带高分子量和低分子量岩藻聚糖硫酸酯为研究对象,采用电刺激造栓法建立大鼠动脉栓塞性脑缺血损伤模型,观察岩藻聚糖硫酸酯对神经行为学评分、脑梗死体积、大脑皮层形态学、血液中花生四烯酸代谢产物(TXB2和6-kelo-PGF1α)、磷脂代谢产物(PA和LPA)和纤溶系统(t-PA和u-PA)的影响。结果静脉注射高分子量和低分子量岩藻聚糖硫酸酯对大鼠栓塞性脑缺血损伤具有很好的保护作用,显著降低神经行为学评分、脑梗死体积和脑皮层神经细胞的损伤,低分子量岩藻聚糖硫酸酯的保护活性是高分子量组分的1/10。岩藻聚糖硫酸酯预防栓塞性脑缺血损伤的作用机理为:抑制TXB2生成,提高6-kelo-PGF1α的水平,抑制LPA的释放,从而抑制血栓的进一步发展;促进t-PA和u-PA的生成从而激活纤溶系统。结论岩藻聚糖硫酸酯在预防栓塞性脑缺血损伤方面具有很好的应用潜质。Objective To study the protective activity of the high molecular weight（HMW）fucoidan and low molecular weight（LMW）fucoidan from Laminaria japonica on the thromboembolic cerebral ischemia injury and possible action mechanism.Methods With the HMW fucoidan and LMW fucoidan fromLaminaria japonicaas the research objectives,the thromboembolic cerebral ischemia injury model was induced by the electricity-stimulated carotid thrombosis in rats,and intravenous administration method was adopted.After injection,the neurological grade evaluation,volume of cerebral infraction,morphology of brain cortex and the content of TXB2,6-keto-PGF1α,t-PA,u-PA,PA and LPA in the blood were measured.Results HMW fucoidan and LMW fucoidan fromLaminaria japonica were effective in preventing the thromboembolic cerebral ischemia injury.Intravenous administration of HMW fucoidan and LMW fucoidan significantly decreased the scores of neurological grade,volume of cerebral infraction and the damage of cerebral cortex neurons,accompanied with alleviates of cerebral edema injury induced by thromboembolic cerebral ischemia in rats.Our results showed that the protective activity of LMW fucoidan was only 10% of HMW fucoidan.Under the effective protection concentration,the protective mechanism on the thromboembolic cerebral ischemia injury of HMW fucoidan and LMW fucoidan might be ascribe to the inhibition of TXB2 and LPA levels and promotion of 6-keto-PGF1α,tPA and u-PA levels.Conclusion Fucoidan had excellent protective activity on the thromboembolic cerebral ischemia injury in vivo.

关 键 词：岩藻聚糖硫酸酯 低分子量岩藻聚糖硫酸酯 栓塞性脑缺血损伤 

分 类 号：R965[医药卫生—药理学]