Xi Yu¹, Yingjuan Liu², Haoyang Sun³, Yan Zheng¹, Keli Ge¹, Yunliang Guo^1,, Weiping Zhu^1,

Objective: To explore the therapeutic effect and possible mechanism of low molecular weight align--guluronic acid (PG) on the copper-loaded mice, so as to provide a new idea for the prevention and treatment of Wilson's disease. Methods: Fifty healthy male Kunming mice were fed copper-loaded diet to establish the copper-loaded mouse model. The mice in treatment group were given different concentrations of PG by gavage, while the mice in control group were orally given same amount of normal solution simutaneously 1 time per day for 60 days. The neurobehavioral function of mice was evaluated by animal behavior; the liver function indexes of mice such as serum levels of total protein (TP), albumin (ALB) , globulin (GLB) were detected by biochemical assay, and the ratio of ALB/GLB (A/G) was calculated; the expression levels of ceruloplasmin (CER), adenine monophosphate activated protein kinase (AMPK) and phosphorylated-AMPK (p-AMPK) in hepatic cells were detected by Western blotting. Results: Compared with control group, the weight of mice in model (Copper) group decreased significantly (P<0.05); The time of rotating rod shortened significantly (P<0.05) and the climbing time prolonged significantly (P<0.01); The serum level of TB decreased significantly (P<0.05), while the ratio of A/G was significantly increased (P<0.05); The expression of CER enhanced significantly (P<0.05), and the level of p-AMPK/AMPK was significantly increased (P<0.05). After treated with different concentrations of PG, the weight of mice in Copper+PG-H group was significantly higher than that in Copper group (P<0.05); The time of rotating rod prolonged significantly (P<0.01) and the climbing time shortened significantly (P<0.05); The serum level of TB increased significantly (P<0.01), while the ratio of A/G was significantly dropped (P <0.05); The expression of CER reduced significantly (P<0.01) and the level of p-AMPK/AMPK was significantly decreased (P<0.01). Conclusion: PG could adsorb and excrete copper ions, reduce inflammation reaction, improve the hepatic metabolism of copper-loaded mice, so that to act a positive effect on Wilson's disease.

guluronic acid, copper load, ceruloplasmin, phosphorylated-AMPK, mice, liver