The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice.
The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice.
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重组人可溶性血栓调节蛋白治疗志贺毒素相关溶血性尿毒症综合征模型小鼠的疗效。
DOI：
10.1093/ndt/gfv004
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
陶山 和秀
中科院分区：
文献类型：
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作者：
Kobayashi S;Kawasaki Y;Sano H;Mochizuki K;Hosoya M;Kikuta A;陶山和秀，川崎幸彦，宮崎恭平，菅野修人，小野敦史，鈴木雄一，大原信一郎，細矢光亮;陶山 和秀
联合人可溶性血栓调节素（rhTM）是一种很有前景的治疗性天然抗凝血剂，与抗凝血酶、组织因子通路抑制剂和活化蛋白c相当。为了阐明rhTM治疗典型溶血性尿毒症（t-HUS）的疗效，我们研究了单独使用rhTM或载药治疗t-HUS小鼠肾脏损伤的变化。方法用志贺毒素（Stx）和脂多糖（LPS）注射治疗重度和中度t-HUS小鼠。将重度t-HUS小鼠与中度t-HUS小鼠分别分为两个亚组[rhTM亚组（A组）和生理盐水亚组（B组）]和[rhTM亚组（C组）和生理盐水亚组（D组）]。E组和F组分别用rhTM和生理盐水治疗健康小鼠。结果注射Stx2和LPS后80 ~ 90 h， B组小鼠全部死亡，而A组小鼠全部存活。在给药后24小时，rhTM处理的t-HUS小鼠的体重损失、血清肌酐水平、内皮损伤和系膜溶解评分均低于生理盐水处理的t-HUS小鼠。给药后6 h血红蛋白水平和24 h血小板计数A组均高于b组。il - 1β和肿瘤坏死因子(TNF) -α水平在24 h后政府在A组低于b组血清C5b-9levels在24 h后,政府和血清纤维蛋白原降解产物(FDP)在72 h后管理Stx2和LPS组低于A组B.ConclusionsThese结果表明rhTM可能负担得起一个有效的治疗t-HUS模型小鼠进一步通过抑制凝血酶的形成和改善hypercoagulant地位。
BackgroundRecombinant human soluble thrombomodulin (rhTM) is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. In order to clarify the efficacy of rhTM for the treatment of typical hemolytic uremic syndrome (t-HUS), we examined changes in renal damage in t-HUS mice treated with rhTM or vehicle alone.MethodsWe used severe and moderate t-HUS mice injected with shiga toxin (Stx) and lipopolysaccharide (LPS). The severe t-HUS mice were divided into two subgroups [an rhTM subgroup (Group A) and a saline subgroup (Group B)] along with the moderate t-HUS mice [an rhTM subgroup (Group C) and a saline subgroup (Group D)]. Groups E and F were healthy mice treated with rhTM or saline, respectively.ResultsAll mice in Group B died at 80–90 h post-administration of Stx2 and LPS whereas all mice in Group A remained alive. Loss of body weight, serum creatinine level, endothelial injury and mesangiolysis scores at 24 h after administration in the t-HUS mice treated with rhTM were lower than those in t-HUS mice treated with saline. The levels of hemoglobin at 6 h and platelet counts at 24 h after administration in Group A were higher than those in Group B. Serum interleukin (IL)-6, IL-1β and tumor necrotic factor (TNF)-α levels at 24 h after administration in Group A were lower than those in Group B. Serum C5b-9levels at 24 h after the administration and serum fibrinogen degradation product (FDP) at 72 h after the administration of Stx2 and LPS were lower in Group A than in Group B.ConclusionsThese results indicate that rhTM might afford an efficacious treatment for t-HUS model mice via the inhibition of further thrombin formation and amelioration of hypercoagulant status.