Lebedeva E I, Babenka A S, Shchastniy A T
Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, 210009 Republic of Belarus.
Belarussian State Medical University, Minsk, 220116 Republic of Belarus.
Acta Naturae. 2023 Apr-Jun;15(2):50-58. doi: 10.32607/actanaturae.17856.
Developing liver disease treatments, in which fibrosis is a key pathogenetic link, still remains an urgent problem in hepatology. In the present study, the level of mRNA expression and the number of FAP+, α-SMA+, CD45+ cells were analyzed at nine time points of fibrosis and cirrhosis. It was found that in the case of liver fibrosis, the choice of the optimal reference gene depended on the stage of fibrogenesis. When studying the specific stages rather than the entire process in a long-term experiment, it was shown that choosing an optimal reference gene has to be done additionally. In this case, the mRNA expression level should be considered as a marker of liver fibrosis initiation and development but not as that of cirrhosis progression. In the liver, two morphologically heterogeneous populations of myofibroblasts were simultaneously identified as able to synthesize various types of immunohistochemical markers. It was found that the FAP+ cells were the main contributor to the development of portal fibrosis and the initial stages of bridging fibrosis. In the selected experimental model, fibrosis initiation and the development stages preceding parenchyma restructuring were accompanied by a low level of inflammation.
开发以纤维化为关键致病环节的肝病治疗方法,仍是肝病学领域的一个紧迫问题。在本研究中,在纤维化和肝硬化的九个时间点分析了mRNA表达水平以及FAP +、α-SMA +、CD45 +细胞的数量。结果发现,在肝纤维化的情况下,最佳内参基因的选择取决于纤维生成阶段。在长期实验中研究特定阶段而非整个过程时,结果表明必须额外选择最佳内参基因。在这种情况下,mRNA表达水平应被视为肝纤维化起始和发展的标志物,而非肝硬化进展的标志物。在肝脏中,同时鉴定出两种形态学上异质的肌成纤维细胞群体,它们能够合成各种类型的免疫组化标志物。结果发现,FAP +细胞是门脉纤维化发展和桥接纤维化初始阶段的主要促成因素。在所选的实验模型中,实质重组之前的纤维化起始和发展阶段伴随着低水平的炎症。