超声辐照增强重组人可溶性血栓调节蛋白对急性肝衰竭的疗效。
Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure.
机构信息
Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
出版信息
Sci Rep. 2020 Feb 3;10(1):1742. doi: 10.1038/s41598-020-58624-0.
The administration of recombinant human soluble thrombomodulin (rhsTM) significantly improves liver inflammation and increases the survival rate of patients with acute liver failure (ALF). However, rhsTM is dose-dependently correlated to the risk of bleeding. Recently, ultrasound (US) was found to enhance the effect of various drugs. Thus, the present study aimed to determine the enhancement effect of US irradiation on rhsTM in ALF. rhsTM (1 mg/kg) and US (1 MHz, 0.3 W/cm) were irradiated to the liver of lipopolysaccharide/D-galactosamine-induced ALF mice model. The post-treatment aspartate aminotransferase, alanine aminotransferase, and high-mobility group box 1 levels were significantly lower in the rhsTM + US group than in the rhsTM alone group. Histopathological findings revealed significantly reduced liver injury and apoptosis in the rhsTM + US group. By contrast, US irradiation had no effect on rhsTM and TNF-α concentration in the liver tissue. In conclusion, US irradiation enhanced the effect of rhsTM in the ALF mice model. However, further studies must be conducted to determine the exact mechanism of such enhancement effect.
重组人可溶性血栓调节蛋白（rhsTM）的给药显著改善了急性肝衰竭（ALF）患者的肝脏炎症，并提高了患者的生存率。然而，rhsTM 的剂量与出血风险呈正相关。最近，人们发现超声（US）可以增强各种药物的作用。因此，本研究旨在确定 US 照射对 ALF 中 rhsTM 的增强作用。将 rhsTM（1mg/kg）和 US（1MHz，0.3W/cm）照射到脂多糖/半乳糖胺诱导的 ALF 小鼠模型的肝脏中。与 rhsTM 单独组相比，rhsTM+US 组的天冬氨酸转氨酶、丙氨酸转氨酶和高迁移率族蛋白 1 水平的治疗后明显降低。组织病理学检查结果显示，rhsTM+US 组的肝损伤和细胞凋亡明显减少。相比之下，US 照射对 rhsTM 和肝组织中 TNF-α浓度没有影响。综上所述，US 照射增强了 rhsTM 在 ALF 小鼠模型中的作用。然而，必须进行进一步的研究以确定这种增强作用的确切机制。
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