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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

摘要:

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120 min,再灌注60 min.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1000 ng/kg、100 ng/kg及10 ng/kg静脉注射,随后10 ng/( kg·min)、l ng/( kg·min)及0.1nig/( 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.各组间基本情况、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±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<0.0l);中剂量TFPI-1组NR严重程度明显低于对照组(P<0.0l)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.

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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 min,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 thenl0 ng/kg,1 ng/kg and 0.1 ng/kg per minute infusion 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.

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