Abstract:

Objective

To investigate the mechanisms underlying gallstone formation and liver injury induced by the lithogenic diet using a mouse model.

Methods

Twelve C57BL/6J mice were divided into two groups by random number table method： stone-forming group and control group， with six mice in each group.The stone-forming group was fed a lithogenic diet that promoted gallstone formation to establish a model of gallstone-induced liver injury， while the control group received a regular diet.Liver tissues were stained with hematoxylin-eosin staining （HE） and immunohistochemical staining （IHC）， and analyzed using Western blotting （WB）， quantitative real-time PCR （qPCR）， enzyme linked immunosorbent assay （ELISA），flow cytometry， and other techniques.

Results

Compared to the mice in the control group， those in the stone-forming group exhibited gallstones.Pathological examination of their livers revealed significant liver injury.Additionally， levels of serum alkaline phosphatase （ALP）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， bilirubin， and bile acid （BA） were significantly elevated.The mRNA levels of nitric oxide synthase 2 （NOS2） and interleukin-1β （IL-1β） were significantly increased （P＜0.001）， and the expression levels of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in AML12 cells were significantly increased （P＜0.000 1）.Activation of the nuclear factor kappa-B （NF-κB） signaling pathway in the liver was observed along with polarization towards M1-type macrophages.

Conclusion

The consumption of a lithogenic diet leads to gallstone formation and subsequent liver injury through promoting M1-type macrophage polarization which further mediates hepatocyte damage.

Key words: Lithogenic diet, Cholecystolithiasis, Liver injury, Macrophage polarization, NF-κB signaling pathway