Melatonin attenuates cholestatic liver injury by improving bile acid metabolism in mice

Objective To explore the mechanism of melatonin (Mel) alleviating cholestatic liver injury in a mouse cholestasis model induced by cholic acid (CA) feeding. Methods A total of 15 8-week-old male C57BL/6J mice were randomly divided into control group, 1%CA group, and 1%CA+Mel group, with 5 animals in each group. The control group was fed with normal chow diet, and the other 2 groups were fed with a diet containing 1%CA for 14 d to construct a model of cholestasis, and intraperitoneal injection with 100 mg/kg Mel was given to the mice from the 1%CA+Mel group. Immunohistochemical assay of α-SMA was applied for the liver tissues in the 1%CA group and the 1%CA+Mel group. The mRNA expression levels of fibrosis-related indicators in mouse liver tissue were examined by RT-qPCR. Liquid chromatography tandem mass spectrometry (LC-MS/MS) and automated biochemical analyzer were used to detect the contents of bile acids in the liver tissues and the serum of mouse, respectively. Then real-time qPCR and Western blotting were applied to detect the expression of bile acid synthesis and liver detoxification enzymes related indicators at mRNA and protein levels, respectively, to further investigate the mechanism of bile acid metabolism. Results Compared with the 1%CA group, the mRNA levels of liver fibrosis indicators (such as Tgfβ1, ColⅠa1, ColⅡa1 and α-SMA) were significantly reduced (P