Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure
Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure
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DOI：
10.1038/s41598-020-58624-0
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发表时间：
2020-02-03
影响因子：
4.6
通讯作者：
Ishikura, Hiroyasu
中科院分区：
文献类型：
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作者：
Hoshino, Kota;Nakamura, Yoshihiko;Ishikura, Hiroyasu
重组人可溶性凝血调节素（rhsTM）可显著改善肝脏炎症，提高急性肝衰竭（ALF）患者的生存率。然而，rhsTM与出血风险呈剂量依赖性相关。最近，超声（US）被发现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 （1 mg/kg）和US （1 MHz, 0.3 W/cm(2)）照射到脂多糖/ d -半乳糖胺诱导的ALF小鼠肝脏。rhsTM + US组治疗后的天冬氨酸转氨酶、丙氨酸转氨酶和高迁移率组1水平显著低于rhsTM单独治疗组。组织病理学结果显示，rhsTM + US组肝损伤和细胞凋亡明显减少。相比之下，US照射对肝组织中rhsTM和tnf - α浓度无影响。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来确定这种增强效应的确切机制。
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(2)) 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-alpha 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.