国产替罗非班对兔髂动脉损伤后血小板活化及血栓前状态的影响

Effects of tirofiban on activated-platelet and prethrombotic state in rabbit iliac artery injury models

目的探讨国产替罗非班（欣维宁）对兔髂动脉急性损伤后血小板活化及血栓前状态的影响。方法健康、成年新西兰大白兔40只，实验前8～12h予阿司匹林12mg／kg、氯吡格雷16mg／kg灌胃后禁食。分成替罗非班预处理组（灌胃后即予替罗非班微泵维持至实验结束，Pre-T组）、替罗非班处理组（T组）和安慰剂组（c组）。动物麻醉后用球囊损伤右髂动脉，经静脉输注替罗非班或安慰剂至实验结束。术前、术后取血送检血小板聚集率，可溶性P选择素、6-酮-前列素F1a等血液指标。术中监测损伤处血压变化，部分行髂动脉造影，并制作病理切片，观察血栓形成情况及性质。结果共30只兔完成实验，其中Pre-T组11只，T组13只，c组6只。（1）血液指标：①可溶性P选择素：协方差分析表明，Pre-T组（术前58．1±26．2μg/L，术后53．2±40．2μg／L）与C组（术前29．7±13．7μg/L，术后62．7±22．4μg／L）或与T组（术前24．8±14．3μg／L，术后53．5±27；7μg／L）间手术前后可溶性P选择素水平变化的差异有统计学意义（P均〈0．05），而T组和C组间差异无统计学意义。②6-酮-前列素F1α：协方差分析结果表明，Pre-T组（术前116．2±11．0ng／L，术后104．8±13．5ng／L）与C组（术前109．1±14．6ng／L，术后70．7±20．5ng／L）或与T组（术前117．0±24．5ng／L，术后86．0±17．2ng／L）间手术前后6-酮-前列素F1α水平变化的差异有统计学意义（P均〈0．05），而T组和C组间差异无统计学意义。③血小板聚集率：Pre-T组（术前87．0％±11．6％，术后48．4％±7．7％）与C组（术前42．7％±15．3％，术后37．5％±28．8％）手术前后的变化之差异有统计学意义（P〈0．05），而T组与其他两组间未见显著差异。（2）局部血压变化：Pre-T组兔子右髂动脉的收缩压、舒张压无明显变化，而C组、T组则较术前均大幅度下降，但T组两者相等所需的时间有延长趋势。（3）血管造影及病理学：Pre-T组造影示血管通畅；虽也有血管壁损伤，但管腔内未见血栓形成。而T组、C组术中造影均可见血栓影；受损髂动脉均可见内皮细胞破坏和内弹性膜的撕裂，管腔内均形成巨大的“白色血栓”。结论替罗非班能有效地抑制血小板活化，改善血栓前状态，充分预处理获益更大。

Objective To investigate the effects of homemade tirofiban on activated-platelet and prethrombotic state in rabbit model of iliac artery injury by balloon angioplasty. Methods Forty New Zealand white rabbits, lavaged with aspirin （ 12 mg/kg） and clopidogrel（16mg/kg） 8 - 12hs before the experiment, followed by abrosia, were divided into 3 groups. The iliac artery injury models were set up successfully only in 30 out of the forty rabbits. Rabbits in the pre-treatment group （ n = 11 ） received homemade tirofiban right after being lavaged and the drug was given to the treatment group （n = 13 ） later after the lilac artery was injured by PTCA balloon. Placebo was given to the control （n =6） after the injury. Blood samples were drawn before and after the procedure for platelet aggregation, sP-selectin and 6-Keto- PGF1α analysis. Changes in iliac systolic blood pressure （SBP） and diastolic blood pressure （DBP） were monitored throughout the operation. Iliac arteriography and pathological study were carried out in some animals for analysis of the composition of thrombus. Results （ 1 ） The sP-selectin levels were different between the pre-treatment group and the treatment group （ 58. 1 ＋ 26. 2 μg/L vs 24. 8 ± 14. 3 μg/L preoperation; 53. 2 ±40. 2 μg/L vs 53.5 ± 27. 7 μg/L pest-operation, respectively, P 〈 0. 05 ） ; as well as between the pre-treatment group and the control （29. 7 ± 13.7 μg/L pre-operation and 62. 7 ±22. 4 μg/L post-operation, P 〈 0.05 ）. There were no differences in SP-selectin levels between the treatment group and the control through covariance analysis. （2） Differences were also found in 6-keto-PGF1α levels between the pre-treatment group and the treatment group （ 116. 2 ± 11.0 ng/L vs 117. 0 ± 24. 5 ng/L pre-operation and 104. 8 ± 13.5 ng/L vs 86. 0 ± 17.2 ng/L post operation, respectively, P 〈 0. 05 ） ; as well as between the pre-treatment group and the control （ 109. 1 ± 14. 6 ng/L pre-operation and 70. 7 ± 20. 5 ng/L postoperation, P 〈 0.05 ）. No differences existed between the treatment group and the control. （3） No obvious changes in blood pressure were recorded in the pre-treatment group which dropped significantly in the treatment group and the control after the procedure. （4） Besides the pre-treatment group, thrombi were found both in the treatment group and the control under arteriography. Pathological study further revealed that the thrombi were mainly ＂white thrombi＂ and with severe endothelia injury of the iliac artery. Injury was also observed on the endothelia in the pre-treatment group under microscope but without thrombus formation. Conclusion Tirofiban can depress the progress of platelet activation and ameliorate the prethrombotic state. Pre-treatment with tirofiban may enhance thse benefits.