Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio, 100, São Paulo, SP, 04044-020, Brazil.
Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, 04044-020, Brazil.
Sci Rep. 2021 Jun 29;11(1):13475. doi: 10.1038/s41598-021-92745-4.
The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His (containing a histidine tail) in an experimental venous thrombosis model of vena cava (VC) ligature in rats, comparing to heparin. We evaluate the effects of the inhibitors (native or recombinant) or heparin on the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human and rat plasmas. The rats undergoing treatment received a saline solution or increasing concentrations of rBbCI-His, heparin, or a mixture of both. After 4 h of ligature VC, thrombus, if present was removed and weighed. aPTT, PT, and cytokines were measured in blood collected by cardiac puncture. aPTT, PT, and bleeding time (BT) were also measured at the time of VC (vena cava) ligature. rBbCI-His (0.45 or 1.40 mg/kg) does not alter aPTT, PT or BT. No differences in coagulation parameters were detected in rBbCI-His treated rats at the time of VC ligature or when the thrombus was removed. There was a significant decrease in the weight of thrombus in the animals of the groups treated with the rBbCI-His (1.40 mg/kg), with the rBbCI-His mixture (1.40 mg/kg) + heparin (50 IU/kg) and heparin (100 IU/kg) in relation to control group (saline). The growth-related oncogene/keratinocyte chemoattractant (GRO/KC) serum levels in rats treated with rBbCI-His (1.40 mg/kg) or heparin (200 IU/kg) were reduced. In the experimental model used, rBbCI-His alone had an antithrombotic effect, not altering blood clotting or bleeding time.
植物蛋白酶抑制剂 BbCI(紫荆胰蛋白酶抑制剂)具有抑制弹性蛋白酶、组织蛋白酶 G 和 L 以及蛋白酶 3 的抗炎作用。在这里,我们在大鼠腔静脉(VC)结扎的实验性静脉血栓模型中研究了重组 rBbCI-His(含有组氨酸尾巴),并与肝素进行了比较。我们评估了抑制剂(天然或重组)或肝素对人血浆和大鼠血浆中活化部分凝血活酶时间(aPTT)和凝血酶原时间(PT)的影响。接受治疗的大鼠接受生理盐水溶液或增加浓度的 rBbCI-His、肝素或两者的混合物。结扎 VC 后 4 小时,取出并称重血栓。通过心脏穿刺采集血液测量 aPTT、PT 和细胞因子。还在 VC(腔静脉)结扎时测量 aPTT、PT 和出血时间(BT)。rBbCI-His(0.45 或 1.40 mg/kg)不改变 aPTT、PT 或 BT。在 VC 结扎时或取出血栓时,rBbCI-His 治疗的大鼠的凝血参数没有差异。用 rBbCI-His(1.40 mg/kg)、rBbCI-His 混合物(1.40 mg/kg)+肝素(50 IU/kg)和肝素(100 IU/kg)治疗的动物血栓重量显著减少与对照组(生理盐水)相比。rBbCI-His(1.40 mg/kg)或肝素(200 IU/kg)治疗的大鼠血清中生长相关癌基因/角质细胞趋化因子(GRO/KC)水平降低。在使用的实验模型中,rBbCI-His 单独具有抗血栓作用,不改变凝血或出血时间。