Internal Medicine Department, Henan University of Chinese Medicine, Zhengzhou, China.
Hepatobiliary Spleen and Stomach Department, Henan Hospital of Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
IUBMB Life. 2020 Jul;72(7):1349-1363. doi: 10.1002/iub.2256. Epub 2020 Feb 26.
Recently, impacts of microRNAs have been unraveled in human diseases, and we aimed to confirm the role of miR-30b/30d in fulminant hepatic failure (FHF). Expression of miR-30b/30d and CEACAM1 in serum of FHF patients and healthy people was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Mice FHF models were established by injection of D-Galn and lipopolysaccharide, and were treated with miR-30b/30d mimics. Oxidative stress, liver injury, and inflammatory reaction in mouse liver tissues were measured using oxidative stress-related factor kits, hematoxylin-eosin staining and enzyme-linked immunosorbent assay, respectively. Moreover, cell cycle distribution and apoptosis of hepatocytes of mice were determined by flow cytometry, and the target relation between miR-30b/30d and CEACAM1 was confirmed by bioinformatic method and dual luciferase reporter gene assay. MiR-30b/30d expression was positively, and CEACAM1 expression was negatively related to prognosis of FHF patients. Up-regulation of miR-30b/30d attenuated oxidative stress, liver injury, and inflammatory reaction, and improved survival rate of FHF mice. Furthermore, elevated miR-30b/30d ameliorated apoptosis and cell cycle arrest of hepatocytes of FHF mice. CEACAM1 was a target gene of miR-30b/30d. This study highlights that up-regulated miR-30b/30d attenuates the progression of FHF by targeting CEACAM1, which may be helpful to FHF treatment.
最近，微小 RNA 对人类疾病的影响已经被揭示出来，我们旨在确认 miR-30b/30d 在暴发性肝衰竭（FHF）中的作用。通过逆转录定量聚合酶链反应（RT-qPCR）和 Western blot 分析测量 FHF 患者和健康人血清中的 miR-30b/30d 和 CEACAM1 的表达。通过注射 D-Galn 和脂多糖建立小鼠 FHF 模型，并使用 miR-30b/30d 模拟物进行治疗。使用氧化应激相关因子试剂盒、苏木精-伊红染色和酶联免疫吸附测定分别测量小鼠肝组织中的氧化应激、肝损伤和炎症反应。此外，通过流式细胞术测定小鼠肝细胞的细胞周期分布和凋亡，通过生物信息学方法和双荧光素酶报告基因测定确认 miR-30b/30d 与 CEACAM1 的靶关系。miR-30b/30d 的表达与 FHF 患者的预后呈正相关，而 CEACAM1 的表达与 FHF 患者的预后呈负相关。上调 miR-30b/30d 可减轻 FHF 小鼠的氧化应激、肝损伤和炎症反应，并提高 FHF 小鼠的生存率。此外，上调的 miR-30b/30d 改善了 FHF 小鼠肝细胞的凋亡和细胞周期阻滞。CEACAM1 是 miR-30b/30d 的靶基因。这项研究强调，上调 miR-30b/30d 通过靶向 CEACAM1 减轻 FHF 的进展，这可能有助于 FHF 的治疗。
