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为证实重组人体血栓调节素(rhTM)对鼠实验性血栓的抗栓效果,作者采用的rhTM 为可溶性TMD_(123),后者表达在中国产鼠卵巢细胞,从条件培养基中提纯,由含表皮生长因子(EGF)样结构的3种细胞外决定簇(决定簇1,2和3)组成,对凝血酶的亲和性与天然TM 基本相近,延长凝血酶时间呈剂量依赖性。从鼠尾静脉注入埃希氏大肠杆菌的脂多糖(LPS)诱发血栓形成。试验组同时注入TMD_(123)250万单位/kg 和LPS 50mg/kg,对照组用生理盐水代替TMD_(123)。注入后抽血查aPTT、纤维蛋白原(Fg)、FDP 和血小板数(BPC)。组织学检查采用PTAH 染色法观察肾、肝及肺组织有无纤维蛋白沉积,用兔抗鼠TM 多克隆抗体由ABC 法作TM 染色。凝血检查结果:单独注入LPS 后BPC、Fg 显著减少,aPTT 明显延长,FDP 明显增高,符合弥散性血管内凝血(DIC)的改变。同时注射与未注射TMD_(123)组凝血象比较,前者Fg、BPC、aPTT 和FDP 均有显著改善。
To confirm the antithrombotic effect of recombinant human thrombomodulin (rhTM) on experimental thrombosis in rats, the author used rhTM as soluble TMD_(123), which was expressed in Chinese mouse ovary cells and purified from conditioned media. The epidermal growth factor (EGF)-like structure consists of three extracellular determinants (determinants 1, 2 and 3). The affinity for thrombin is similar to that of natural TM, and prolongs thrombin time in a dose-dependent manner. Lipopolysaccharide (LPS) injected into Escherichia coli from the tail vein of rats induces thrombosis. In the test group, 2.5 million units/kg of TMD_(123)/kg and 50 mg/kg of LPS were injected at the same time. The control group used saline instead of TMD_(123). After injection, blood was drawn for aPTT, fibrinogen (Fg), FDP, and platelet count (BPC). Histological examination of PTAH staining was used to observe the presence of fibrin deposition in kidney, liver, and lung tissues. A rabbit anti-mouse TM polyclonal antibody was used for TM staining by ABC method. Blood coagulation test results: After injecting LPS alone, BPC, Fg significantly decreased, aPTT significantly prolonged, and FDP increased significantly, consistent with changes in disseminated intravascular coagulation (DIC). At the same time, the Fg, BPC, aPTT, and FDP were significantly improved in both the injected and uninjected TMD_(123) groups.