Department of Surgery , National Taiwan University Hospital , Taipei 100 , Taiwan.
Center of Precision Medicine, College of Medicine , National Taiwan University , Taipei 100 , Taiwan.
Mol Pharm. 2019 Mar 4;16(3):1092-1104. doi: 10.1021/acs.molpharmaceut.8b01108. Epub 2019 Feb 13.
There are very limited clinically viable treatment options for acute liver failure, a life-threatening condition that rapidly progresses to loss of liver function. In this study, we aim to evaluate the therapeutic potential of UCBP for acute liver failure induced in a rat model by D-galactosamine (GalN). F344 rats were randomly divided into two groups (control and UCBP-treated) after GalN injection. The therapeutic effects of UCBP were evaluated based on survival rate, H&E staining, TUNEL, PCNA staining, and in vivo BrdU labeling. Hepatocyte proliferation and the therapeutic mechanisms of UCBP were examined with BrdU and Western blot assay in vitro. The survival rate in the UCBP-treated group was found to be increased compared to the control group (85 vs 55%, P = 0.029). UCBP treatment significantly decreased apoptosis and increased cell proliferation. These effects may be secondary to specific bioactive molecules in UCBP. In vitro experiments revealed that adiponectin is one of the key biologically active components of UCBP in facilitating this result and promoting hepatocyte proliferation. Furthermore, this effect is mediated by p38/ERK mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, this uncomplicated and clinically accessible approach may serve as effective bridge therapy for acute liver failure.
对于急性肝衰竭这种危及生命的疾病,目前临床上可行的治疗方法非常有限,这种疾病会迅速发展为肝功能丧失。在这项研究中,我们旨在评估 UCBP 在半乳糖胺(GalN)诱导的大鼠急性肝衰竭模型中的治疗潜力。F344 大鼠在 GalN 注射后随机分为两组(对照组和 UCBP 治疗组)。根据生存率、H&E 染色、TUNEL、PCNA 染色和体内 BrdU 标记评估 UCBP 的治疗效果。体外 BrdU 和 Western blot 检测肝细胞增殖和 UCBP 的治疗机制。与对照组相比,UCBP 治疗组的生存率有所提高(85%对 55%,P=0.029)。UCBP 治疗可显著减少细胞凋亡并增加细胞增殖。这些作用可能是 UCBP 中特定生物活性分子的继发作用。体外实验表明,脂联素是 UCBP 促进肝细胞增殖的关键生物活性成分之一。此外,这种作用是通过 p38/ERK 丝裂原活化蛋白激酶(MAPK)信号通路介导的。因此,这种简单且临床可及的方法可能成为急性肝衰竭的有效桥接治疗方法。