Hepatic fibrosis is a reversible scaring response to chronic liver injury. MicroRNA (miR)-129-5p might regulate fibrosis-related gene expression. This study is performed to decipher, potential of miR-129-5p to influence the progression of hepatic fibrosis in a carbon tetrachloride (CCl₄) rat model. Rat hepatic fibrosis was successfully established by subcutaneous injection of 50% CCl4. RT-qPCR revealed that miR-129-5p was poorly expressed and PEG3 was highly expressed in hepatic fibrosis tissues. As reflected by dual-luciferase reporter gene assay, miR-129-5p targeted and reduced the expression of PEG3. Thereafter, miR-129-5p antagomir or short hairpin RNA against paternally expressed gene 3 (PEG3) was adopted for gain- and loss-of-function assay to determine the molecular regulatory mechanism of miR-129-5p. Moreover, we detected the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins and apoptosis-related factors, and made a serological analysis of the rat serum samples. Results showed that upregulated miR-129-5p or downregulated PEG3 led to reduction of the histological changes of liver cirrhosis and lowered the apoptosis rate, via downstream effects on the NF-κB signaling pathway. Thus, the hepatic fibrosis induced by CCl₄ can be rescued by upregulated miR-129-5p or downregulated PEG3 expression.

肝纤维化是对慢性肝损伤的可逆性惊吓反应。MicroRNA (miR)-129-5p 可能调节纤维化相关基因的表达。本研究旨在解读 miR-129-5p 在四氯化碳 (CCl ₄) 大鼠模型。通过皮下注射 50% CCl4 成功建立大鼠肝纤维化。RT-qPCR 显示 miR-129-5p 在肝纤维化组织中低表达而 PEG3 高表达。正如双荧光素酶报告基因检测所反映的那样，miR-129-5p 靶向并降低了 PEG3 的表达。此后，采用 miR-129-5p antagomir 或针对父本表达基因 3 (PEG3) 的短发夹 RNA 进行功能获得和损失测定，以确定 miR-129-5p 的分子调控机制。此外，我们检测了核因子κB（NF-κB）信号通路相关蛋白和凋亡相关因子的表达，并对大鼠血清样品进行了血清学分析。结果表明，上调 miR-129-5p 或下调 PEG3 通过对 NF-κB 信号通路的下游影响导致肝硬化的组织学变化减少并降低细胞凋亡率。因此，CCl 诱导的肝纤维化₄可以通过上调 miR-129-5p 或下调 PEG3 表达来挽救。