Shahrour Khaled, Keck Rick, Jankun Jerzy
Department of Urology, the University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
Department of Urology, the University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA ; Department of Clinical Nutrition, Medical University of Gdańsk, Debinki 7, 80-211 Gdańsk, Poland ; Protein Research Chair, Department of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia ; Urology Research Center, Department of Urology, the University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
Biomed Res Int. 2015;2015:392862. doi: 10.1155/2015/392862. Epub 2015 Mar 26.
PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant (P ≤ 0.05) reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds.
纤溶酶原激活物抑制剂-1(PAI-1)通过抑制尿激酶和组织型纤溶酶原激活物(tPA)诱导的纤溶酶原向纤溶酶的转化来防止血凝块溶解。构建了VLHL PAI-1蛋白突变体以将半衰期延长至700多小时。本文的目的是测试VLHL PAI-1对小鼠部分肾切除术中出血的影响。所有动物在静脉输注生理盐水或tPA后进行左半肾切除术。将动物分为四组。第1组输注生理盐水,肾脏也暴露于生理盐水;第2组输注生理盐水,肾脏暴露于PAI-1。第3组输注tPA,肾脏暴露于生理盐水,而第4组输注tPA,肾脏暴露于PAI-1。然后将预先称重的含有PAI-1或生理盐水的纱布敷在肾脏上30分钟。之后对纱布进行称重,并通过从最终重量中减去纱布的预重量来测量失血量。我们观察到,与生理盐水和tPA治疗组相比,PAI-1治疗组的出血有统计学意义的减少(P≤0.05)。基于这些结果,我们提出VLHL PAI-1可用于治疗性地限制肾伤口的血流。