Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
Departments of Electrical Engineering, Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan, 333, Taiwan.
Sci Rep. 2017 May 9;7(1):1638. doi: 10.1038/s41598-017-01769-2.
Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50-63% in groups E and F, to 67-83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.
联合应用聚焦超声（FUS）和神经保护剂 BNG-1，通过 LED 照射在大鼠急性颈内动脉血栓闭塞模型中进行研究，以提高 rt-PA 的溶栓效果。共设立 7 个治疗组，包括（A）静脉推注 0.45mg/kg rt-PA，（B）静脉推注 0.9mg/kg，（C）单纯 FUS 声溶栓，（D）口服 2g/kg BNG-1 共 7 天，（E）A+D，（F）A+C，和（G）A+C+D。共设立 4 个对照组，包括（H）0.45mg/kg rt-PA 20%推注+80%IV 输注+FUS，（I）0.9mg/kg rt-PA 10%推注+90%静脉输注，（J）B+C，（K）B+D。颈内动脉闭塞 7 天后，小动物颈动脉超声和 7T MR 血管造影显示狭窄程度≤50%的再通率，B 组为 50%，I 组为 83%，而 A 组和 C 组为 0%，D 组为 17%。联合治疗使 E 组和 F 组的再通率提高到 50-63%，J 组和 K 组提高到 67-83%，G 组和 H 组提高到 100%。本研究表明，联合应用不同的治疗方法是提高 rt-PA 溶栓效果的一种可行策略。
