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首页> 外文期刊>Transplantation Proceedings >Effect of synthetic protease inhibitor gabexate mesilate on attenuation of coagulant activity and cytokine release in a rat model of islet transplantation
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Effect of synthetic protease inhibitor gabexate mesilate on attenuation of coagulant activity and cytokine release in a rat model of islet transplantation

机译：合成蛋白酶抑制剂甲磺酸阿贝酯对大鼠胰岛移植模型凝血活性和细胞因子释放的影响

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Background: The instant blood-mediated inflammatory reaction (IBMIR), in which the activation of coagulation cascade plays a key role, is one of the serious obstacles to successful islet engraftment. Gabexate mesilate (GM) is well known to elicit anticoagulant and antiinflammatory effects. The aim of this study was to evaluate the effect of GM on syngeneic IBMIR. Methods: Syngeneic rat islet grafts (2.5 IEQ/g) were transplanted intraportally into 2 groups (control group and GM group; n = 1011) of streptozotocin-induced diabetic rats. The GM group was injected intravenously with GM for 30 minutes before islet infusion to 1 hour after. The control group was injected with equivalent amount of saline solution. Plasma samples were collected before and 0.5, 1, 3, 6, and 24 hours after transplantation, and several proinflammatory mediators, including interleukin-6 and high-mobility group Box 1 were measured. Curative rate, intravenous glucose tolerance test, and insulin amount in the recipients' livers were also evaluated. Results: Little difference was observed in any proinflammatory mediators. Whereas none of the animals in the control group became normoglycemic, 2 of 6 rats transplanted with the same number of islets in the GM group became normoglycemic during the study period. The glucose tolerance response was significantly ameliorated in the GM group compared with the control group (P < 0.001). The insulin amount in the liver of the recipients was considerably higher in the GM group (5.6 ± 4.1 vs 12.6 ± 5.3 ng/IEQ; P <.05). Conclusions: These data suggest that GM improves islet engraftment not through suppressing the proinflammatory cytokines but as an anticoagulant. We therefore think that GM could be a useful anticoagulant to control IBMIR induced in clinical islet transplantation, although antiinflammatory reagents are considered to be needed for the ideal regimen.
机译：背景：瞬时血液介导的炎症反应（IBMIR）（其中凝血级联反应的激活起着关键作用）是成功植入胰岛的严重障碍之一。众所周知，甲磺酸加贝沙酯（GM）具有抗凝和抗炎作用。这项研究的目的是评估GM对同源IBMIR的影响。方法：将同种异体大鼠胰岛移植物（2.5 IEQ / g）经门静脉移植入链脲佐菌素诱导的糖尿病大鼠的两组（对照组和GM组; n = 1011）。 GM组在胰岛输注前30分钟至1小时后静脉内注射GM。对照组注射等量盐溶液。在移植前和移植后0.5、1、3、6和24小时收集血浆样品，并测量了几种促炎介质，包括白介素6和高迁移率组Box 1。还评估了接受者肝脏中的治愈率，静脉葡萄糖耐量试验和胰岛素量。结果：在任何促炎介质中均未观察到差异。对照组中没有动物变成正常血糖，而在GM组中移植了相同数量的胰岛的6只大鼠中有2只在研究期间变成了正常血糖。与对照组相比，GM组的葡萄糖耐量反应明显改善（P <0.001）。 GM组接受者肝脏中的胰岛素含量明显更高（5.6±4.1 vs 12.6±5.3 ng / IEQ; P <.05）。结论：这些数据表明，转基因不是通过抑制促炎细胞因子而是作为抗凝剂来改善胰岛的植入。因此，尽管认为理想的治疗方案需要使用抗炎药，但我们认为GM可能是控制临床胰岛移植中诱导的IBMIR的有用抗凝剂。

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