烙铁头血小板活化素延长豚鼠到大鼠的异种移植心脏存活时间

研究烙铁头m小板活化索(TMVA)对大鼠血小板聚集的抑制作用以及对豚鼠 到大鼠的异种移植心存活时间的影响。方法(1)TMVA对血小板聚集率的影响：将Wistar大鼠随 机分为3组，每组5只，各组经阴茎背静脉注射不同剂量(20、50或100 pg／kg)的TMVA，于注射前 以及注射后0．5 h和24 h时抽血，测定血小板聚集率。(2)TMVA对豚鼠到大鼠的异种移植心存活 时间的影响：以豚鼠为供者，Wistar大鼠为受者，制作颈部异位心脏移植模型，实验组于移植心恢复 血液循环前0．5 h经静脉给予TMVA 50弘g／kg，另设不使用TMVA的对照组。观察移植心的存活 时间，停跳后的移植心组织行病理学检查，并用放射免疫法检测心肌组织内6一酮一前列腺素F，。 (6一keto-PGF。。)及血栓素B2(TXt笺)的含量。结果(1)静脉给予5()或100 pg／kg的TMVA后0．5 h即能完全抑制血小板聚集。(2)实验组移植心的存活时间为1()～135 min，中位数为42 min；对照组 为4～16 min，中位数为5 min，两组比较，差异有统计学意义(P

TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival

In xenotransplantation, donor endothelium is the first target of immunological attack. Activation of the endothelial cell by preformed natural antibodies leads to platelet binding via the interaction of the glycoprotein (GP) Ib and von Willebrand factor (vWF). TMVA is a novel GPIb-binding protein purified from the venom of Trimeresurus mucrosquamatus. In this study, the inhibitory effect of TMVA on platelet aggregation in rats and the effect on discordant guinea pig-to-rat cardiac xenograft survival were investigated. Three doses (8, 20 or 40 mug/kg) of TMVA were infused intravenously to 30 rats respectively. Platelet aggregation rate was assayed 0.5, 12, and 24 h after TMVA administration. Wister rats underwent guinea pig cardiac cervical heterotopic transplantation using single dosing of TMVA (20 mug/kg, i.v., 0.5 h before reperfusion). Additionally, levels of TXB2 and 6-keto-PGF(1alpha) within rejected graft tissues were determined by radioimmunoassay. Treatment with TMVA at a dose of 20 or 40 mug/kg resulted in complete inhibition of platelet aggregation 0.5 h after TMVA administration. Rats receiving guinea pig cardiac xenografts after TMVA therapy had significantly prolonged xenograft survival. Histologic and immunopathologic analysis of cardiac xenografts in TMVA treatment group showed no intragraft platelet microthrombi formation and fibrin deposition. Additionally, the ratio of 6-keto-PGF(1alpha) to TXB2 in TMVA treatment group was significantly higher than those in control group. We conclude that the use of this novel GPIb-binding protein was very effective in preventing platelet microthrombi formation and fibrin deposition in a guinea pig-to-rat model and resulted in prolongation of xenograft survival. The increased ratio of PGI(2)/TXA(2) in TMVA treatment group may protect xenografts from the endothelial cell activation and contribute to the prolongation of xenograft survival.