Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
World J Emerg Med. 2010;1(2):126-31.
Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy.
A total of 30 adult beagles were equally divided into 5 groups after thrombi: vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy.
In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)% in the medium-dose rtPAm group and (0.7+0.4)% in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group.
rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.
新型冠脉溶栓药物研发方兴未艾。新型药物突变重组组织型纤溶酶原激活剂（rtPAm）是通过改变与纤溶酶原激活物抑制剂（PAI）-1的结合位点数从而减少降解，使 tPA 发生突变的产物。体外试验已经证实，在不存在 PAI 的情况下，rtPAm 的活性比 rtPA 高得多。本研究旨在观察突变重组组织型纤溶酶原激活剂（rtPAm）在冠脉溶栓治疗中的疗效。
血栓形成后，将 30 只成年比格犬等分为 5 组：对照组、尿激酶组、rtPAm 低剂量组、rtPAm 中剂量组和 rtPAm 高剂量组。溶栓治疗后观察溶栓效果和心肌梗死情况。
尿激酶组再通时间为（15.8±3.8）min。90min 时，4 只犬显示 TIMI2 级血流，2 只犬显示 TIMI3 级血流，4 只犬再闭塞。rtPAm 低剂量组再通时间为（15±4.5）min；90min 时，2 只犬显示 TIMI2 级血流，4 只犬显示 TIMI3 级血流，2 只犬再闭塞。rtPAm 高剂量组再通时间为（7.5±2.6）min。90min 时无一例再闭塞。中剂量 rtPAm 组梗死面积为（2.1+0.9）%，高剂量 rtPAm 组为（0.7+0.4）%，均明显小于低剂量 rtPAm 组。中剂量和高剂量 rtPAm 组的血小板聚集率明显低于尿激酶组。
rtPAm 可能是一种具有血小板靶向纤溶和抗血小板聚集活性的溶栓药物。
