关键词: 淫羊藿苷, 急性肝损伤, 抗炎, 抗氧化, 内质网应激, 程序性坏死

Abstract: BACKGROUND: Icariin, with antiinflammatory, antioxygenatory and immunoregulatory effects, can be a potential drug for preventing and treating acute liver injury.
OBJECTIVE: To investigate the protective effect and possible mechanism of icariin in mice with acute liver injury induced by carbon tetrachloride.
METHODS: Thirty-two Kunming mice were equally and randomly divided into the following groups: normal, model, low-dose icariin and high-dose icariin groups. The low- and high-dose icariin groups were continuously gavaged with icariin (100 and 200 mg/kg, respectively) once a day for 7 continuous days. The normal group and model group were injected with physiological saline (10 mL/kg) at the same time point. After the last administration, all the groups except for the normal group were injected with carbon tetrachloride to induce acute liver injury. The mice were killed 24 hours later, and the liver index was detected. Serum levels of alanine aminotransferase and aspartate aminotransferase were detected by automated biochemical analysis. Tumor necrosis factor α and interleukin 6 levels in serum were detected using ELISA. The levels of superoxide dismutase, glutathione peroxidase and malondialdehyde in liver tissue were detected through a reagent kit. The histopathology changes of the liver were observed by hematoxylin-eosin staining. TUNEL method was used to detect the apoptosis in hepatocytes. Western blot was performed to detect the expression levels of glucose-regulated protein 78 kDa, endoplasmic reticulum stress-related protein (C/-EBP homologous protein), mixed lineage kinase domain-like protein and Caspase-3 in liver tissue.
RESULTS AND CONCLUSION: Compared with the normal group, the liver index and serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor α and interleukin 6 were increased in the model group (P < 0.05). Compared with the model group, the above indexes were decreased in the low-dose and high-dose icariin groups (P < 0.05). Compared with the normal group, the activities of superoxide dismutase and glutathione peroxidase in the liver tissue of mice were decreased in the model group (P < 0.05) and the level of malondialdehyde was increased (P < 0.05). Compared with the model group, the activities of superoxide dismutase and glutathione peroxidase were increased in the low- and high-dose icariin groups (P < 0.05) and the level of malondialdehyde was decreased (P < 0.05). Hematoxylin-eosin and TUNEL staining showed that mice in the model group had severe structural destruction of liver tissue, extensive necrosis of hepatocytes and high apoptotic rate of hepatocytes, while the structural destruction of liver tissue and the area of necrosis of hepatocytes in the low- and high-dose icariin groups were significantly milder than those in the model group, and the apoptotic rate of hepatocytes was lower than that in the model group (P < 0.05). Western blot assay showed that the protein expression of glucose-regulated protein 78 kDa, C/-EBP homologous protein, mixed lineage kinase domain-like protein and Caspase-3 in liver tissue of mice in the model group was increased compared with that in the normal group (P < 0.05), while the expression levels of these proteins in liver tissue of mice were significantly reduced after low- and high-dose icariin intervention (P < 0.05). To conclude, icariin can produce a protective effect against carbon tetrachloride-induced acute liver injury, and its mechanism may be related to the regulation of endoplasmic reticulum stress and reduction of programmed necrosis.

Key words: icariin, acute liver injury, antiinfammation, antioxygenation, endoplasmic reticulum stress, programmed necrosis