Luo Jing-guang, Chen Yun-dai, Tian Feng, Wang Chang-hua, Lü Yuan, Yang Xiu-xiu, Lü Shu-zheng
Department of Cardiology, Chinese People's Liberation Army General Hospital, Beijing 100863, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Dec;37(12):1113-8.
To investigate the role of plasma tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI-1) level and to observe the effect of extrinsic TFPI-1 on no-reflow (NR) in a rabbit model of ischemia/reperfusion.
Rabbits were randomized into four groups (n = 10 each): ischemic- reperfusion group (IR, subjected to 120 minutes of coronary artery occlusion and followed by 60 minutes of reperfusion); ischemic- reperfusion TFPI-1 group (100 ng/kg bolus and 1 ng x kg(-1) x min(-1) infusion during reperfusion); ischemic group (subjected to 180 minutes of coronary artery occlusion) and sham group. The NR area and ischemic area were determined by thioflavin S and Evan's blue staining in vivo. Plasma TF and TFPI-1 levels were measured before operation, before and at 120 minutes post coronary artery ligation, 10 and 60 minutes after reperfusion by ELISA.
Plasma TF and TFPI-1 levels before and at 120 minutes post coronary artery ligation were similar among the four groups (all P > 0.05). At 10 and 60 minutes after reperfusion, the plasma TF levels in the IR group was significantly higher than those in ischemic group and sham group [10 minutes: (20.7 + or - 4.1) pg/ml vs. (13.9 + or - 2.2) pg/ml (P < 0.001), (20.7 + or - 4.1) pg/ml vs. (13.2 + or - 2.6) pg/ml (P < 0.001); 60 minutes: (15.8 + or - 2.6) pg/ml vs. (13.5 + or - 1.6) pg/ml (P < 0.05), (15.8 + or - 2.6) pg/ml vs. (12.1 + or - 0.7) pg/ml (P < 0.001)] while the plasma TFPI-1 levels were similar among IR, ischemic and sham groups at 10 minutes after reperfusion and at 60 minutes after reperfusion (all P > 0.05). TFPI-1 level [(9.7 + or - 1.6) ng/ml] was significantly lower in the IR group than in the ischemic group [(11.6 + or - 1.6) ng/ml, P < 0.05] and sham group [(10.1 + or - 1.3) ng/ml, P < 0.01]. TF mRNA expression in the NR area in IR group was significantly up-regulated compared to the ischemic group (P < 0.05) and sham group (P < 0.001) while TFPI-1 mRNA expression was similar between IR group and ischemic group (P > 0.05). NR severity in the ischemic-reperfusion TFPI-1 group was significantly attenuated compared to IR group (0.39 + or - 0.11 vs. 0.54 + or - 0.06, P < 0.01).
Upregulated TF mRNA expression in the NR area and increased plasma TF level during reperfusion period, reduced plasma TFPI-1 level during reperfusion period as well as attenuated NR severity by extrinsic application of human rTFPI-1 in this model suggested an important role in the pathogenesis of the NR phenomenon.
探讨血浆组织因子（TF）和组织因子途径抑制物-1（TFPI-1）水平的作用，并观察外源性TFPI-1对兔缺血/再灌注模型中无复流（NR）的影响。
将兔子随机分为四组（每组n = 10）：缺血-再灌注组（IR，冠状动脉闭塞120分钟，随后再灌注60分钟）；缺血-再灌注TFPI-1组（再灌注期间静脉推注100 ng/kg，然后以1 ng·kg⁻¹·min⁻¹输注）；缺血组（冠状动脉闭塞180分钟）和假手术组。通过硫黄素S和伊文思蓝染色在体内测定NR面积和缺血面积。在手术前、冠状动脉结扎前、结扎后120分钟、再灌注后10分钟和60分钟，采用酶联免疫吸附测定法（ELISA）检测血浆TF和TFPI-1水平。
四组在冠状动脉结扎前及结扎后120分钟时血浆TF和TFPI-1水平相似（均P > 0.05）。再灌注后10分钟和60分钟时，IR组血浆TF水平显著高于缺血组和假手术组[10分钟：(20.7 ± 4.1) pg/ml比(13.9 ± 2.2) pg/ml（P < 0.001），(20.7 ± 4.1) pg/ml比(13.2 ± 2.6) pg/ml（P < 0.001）；60分钟：(15.8 ± 2.6) pg/ml比(13.5 ± 1.6) pg/ml（P < 0.05），(15.8 ± 2.6) pg/ml比(12.1 ± 0.7) pg/ml（P < 0.001）]，而再灌注后10分钟及60分钟时，IR组、缺血组和假手术组血浆TFPI-1水平相似（均P > 0.05）。IR组TFPI-1水平[(9.7 ± 1.6) ng/ml]显著低于缺血组[(11.6 ± 1.6) ng/ml，P < 0.05]和假手术组[(10.1 ± 1.3) ng/ml，P < 0.01]。与缺血组相比，IR组NR区域内TF mRNA表达显著上调（P < 0.05），与假手术组相比差异极显著（P < 0.001），而IR组与缺血组之间TFPI-1 mRNA表达相似（P > 0.05）。与IR组相比，缺血-再灌注TFPI-1组的NR严重程度显著减轻（0.39 ± 0.11比0.54 ± 0.06，P < 0.01）。
在该模型中，NR区域内TF mRNA表达上调、再灌注期血浆TF水平升高、再灌注期血浆TFPI-1水平降低以及外源性应用人重组TFPI-1减轻NR严重程度，提示其在NR现象发病机制中起重要作用。
