组织因子途径抑制物-1对无复流作用的实验研究

Effect of tissue factor pathway inhibitor-1 on no-reflow phenomenon in rabbit

目的探讨不同剂量外源性重组人组织因子途径抑制物-1（TFPI-1）防治实验性无复流（NR）的作用。方法北京安贞医院实验室，新西兰大白兔52只，结扎回旋支中段120min，再灌注60rain。在再灌注即刻随机（随机数字法）分为对照组及大、中、小剂量TFPI-1组[分别为1000ng／kg、100．g／kg及10ng／kg静脉注射，随后10ng／（kg·min）、1ng／（kg·min）及0．1ng／（kg·min）静脉滴注，n=13只／组]。活体硫磺素s及Evan’s蓝心肌着色测定解剖无复流面积（NA）和缺血面积（IA）。NR严重程度用NA／IA表示。比较不同组别NR严重程度，并观察血栓形成及心肌损伤情况。各组问基本情况、心肌缺血及NR严重程度比较用完全随机设计单因素方差分析，均数两两比较采用LSD检验。结果各组体质量、缺血面积比较差异无统计学意义（P〉0．05）。大、中、小剂量TFPI-1组和对照组NR严重程度分别为（0．210±0．061）、（0．389-4-0．1100、（0．478±0．077）和（0．536±0．061）。大剂量TFPI-1组NR严重程度较其他三组明显减轻（P〈0．01）；中剂量TFPI-1组NR严重程度明显低于对照组（P〈0．01）和小剂量TFPI-1组（P〈0．05）；小剂量TFPI-1组和对照组NR严重程度差异无统计学意义（P〉0．05）。大剂量TFPI—1组血栓形成减少，无复流区心肌组织损伤减轻。结论外源性TFPI-1可显著减轻兔NR严重程度，且随剂量增大作用增强，再灌注时静脉应用TFPI-1可防治NR现象。

Objective To observe the effects of different doses of human recombinant tissue factor pathway inhibitor-1 （ TFPI-1 ） on no-reflow （NR） phenomenon in rabbit. Methods Fifty-two New Zealand white rabbits were subjected to coronary artery occlusion for 120 min and followed by reperfusion for 60 rain, and then were randomly （random number） assigned into four groups： control group, large, moderate and low doses TFPI-1 groups （1000 ng/kg, 100 ng/kg, 10 ng/kg bolus and then10 ng/kg, 1 ng/kg and 0. 1 ng/kg per minute inffusion for maintenance, each group n = 13）. The no-reflow area （NA） and ischemic area （IA） was measured by thioflavin S and Evan＇ s blue, The NR severity was expressed by NA/IA. The difference in NR severity was compared between groups. The thrombi and myocardial injury were observed under light microscope. The infarction and NR severity in different groups were compared by using one-way ANOVA followed by LSD procedure. Results There were no significant differences in IA and body weight among four groups （P 〉 0. 05）. NR severity in the large, moderate, low doses TFPI-1 groups and control group were （0. 210±0. 061 ）, （0. 389 ±0. 110） , （0. 478 ±0. 077） and （0. 536 ±0. 061 ） , respectively. NR severity in the large dose TFPI-1 group was slightest among the four groups （ P 〈 0. 01 ）. NR severity in the moderate dose TFPI-1 group was significantly decreased than that in control group （P 〈 0. 01 ） and in low dose TFPI-1 group （P 〈 0. 05 ）. There was no significant difference in NR severity between the low dose TFPI-1 group and control group （P 〉 0. 05）. There was less thrombus formation and lower grade myocardial injury found in the large dose TFPI-1 group. Conclusion Human rTFPI-1 might lessen NR severity in rabbit in dose-dependent, suggesting the option on human rTFPI-1 for treatment of NR phenomenon.