Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Int J Mol Med. 2018 Aug;42(2):873-882. doi: 10.3892/ijmm.2018.3684. Epub 2018 May 17.
The present study aimed to investigate the role of the C‑sis gene in the apoptosis of hepatocytes in vitro and in the liver function of a rat model of fulminant hepatic failure (FHF). Buffalo rat liver (BRL) cells were treated with hydrogen peroxide (H2O2) to induce apoptosis and then transfected with a C‑sis overexpression vector. A rat model of FHF was established, and C‑sis was overexpressed. The mRNA and protein expression of C‑sis were examined using reverse transcription‑polymerase chain reaction and western blot analyses, respectively. Cell viability was assessed by CCK8, and a TUNEL assay was used to examine cell apoptosis. Flow cytometry was used for cell cycle detection. Hematoxylin and eosin staining was used for histological examination. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also examined in the rats. The results showed that C‑sis was successfully overexpressed in the cells and rat model. Compared with H2O2‑treated BRL cells, the overexpression of C‑sis significantly inhibited cell apoptosis, promoted cell viability, and decreased the expression of cleaved caspase-3. Similar results were observed in the FHF rats treated with the C‑sis overexpression plasmid, compared with those treated with empty plasmids. In addition, in the FHF rats overexpressing C‑sis, histological examination showed that liver injury was alleviated, the levels of ALT and AST were significantly decreased, and mortality rate was significantly decreased, compared with those observed in the rats treated with empty plasmids. In conclusion, the overexpression of C‑sis inhibited the H2O2‑induced apoptosis of BRL cells in vitro, and alleviated liver injury, improved liver function, and decreased mortality rates in rat models of FHF.
本研究旨在探讨 C‑sis 基因在体外肝细胞凋亡和暴发性肝衰竭（FHF）大鼠模型肝功能中的作用。用过氧化氢（H2O2）处理水牛大鼠肝（BRL）细胞以诱导细胞凋亡，然后转染 C‑sis 过表达载体。建立 FHF 大鼠模型并过表达 C‑sis。采用逆转录聚合酶链反应和 Western blot 分析分别检测 C‑sis 的 mRNA 和蛋白表达。通过 CCK8 检测细胞活力，TUNEL 检测细胞凋亡，流式细胞术检测细胞周期，苏木精和伊红染色进行组织学检查。还检测了大鼠丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的水平。结果表明，细胞和大鼠模型中 C‑sis 成功过表达。与 H2O2 处理的 BRL 细胞相比，C‑sis 的过表达显著抑制细胞凋亡，促进细胞活力，并降低 cleaved caspase-3 的表达。在过表达 C‑sis 的 FHF 大鼠中也观察到了类似的结果，与空质粒处理的大鼠相比。此外，在过表达 C‑sis 的 FHF 大鼠中，与空质粒处理的大鼠相比，组织学检查显示肝损伤减轻，ALT 和 AST 水平显著降低，死亡率显著降低。综上所述，C‑sis 的过表达抑制了体外 H2O2 诱导的 BRL 细胞凋亡，并减轻了 FHF 大鼠模型的肝损伤，改善了肝功能，降低了死亡率。
