The effect of Suaeda salsa polysaccharides on necroptosis in liver cells of mice with metabolic-associated fatty liver disease induced by a high-fat diet
昌宇 秦
2026, 47(5):
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Objective Investigating the Effects of Suaeda salsa Polysaccharide on Necroptosis in Hepatocytes of Metabolic-associated Fatty Liver Disease (MAFLD) Mice Induced by a High-Fat Diet. Methods A total of sixty male C57BL/6J mice, aged 6 to 8 weeks, were randomly allocated into six experimental groups: a control group, a high-fat diet-induced model group, and three treatment groups receiving Suaeda salsa polysaccharide at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, along with a positive control group administered atorvastatin (1 mg/kg). Each group consisted of 10 animals. In the experimental design, the control cohort received a standard chow diet, whereas the other experimental groups were maintained on a high-fat dietary regimen. Each intervention group received daily gastric lavage for 12 consecutive weeks, while the control group received daily gastric lavage with an equal volume of distilled water. Observe and record changes in body weight for each group of mice.To evaluate hepatic pathological alterations, liver sections from experimental mice were subjected to Hematoxylin and Eosin (HE) staining. Lipid deposition in hepatic tissues was quantitatively assessed through Oil Red O staining. Serum biochemical parameters including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using an automated biochemical analyzer. Circulating levels of inflammatory cytokines, specifically Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Tumor necrosis factor-α (TNF-α), were quantified via enzyme-linked immunosorbent assay (ELISA). Protein expression profiles of key necroptosis markers, namely receptor-interacting protein kinase 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), and its phosphorylated form (p-MLKL), were analyzed by Western blotting in liver tissue homogenates.Real-time PCR was used to detect the mRNA expression levels of RIP3 and MLKL in mouse liver tissue. Results The experimental animals in the model group demonstrated a statistically significant augmentation in body mass and hepatic index when compared to the control cohort. HE staining revealed marked fatty degeneration in the livers of mice in the model group. Oil Red O staining revealed extensive lipid accumulation within hepatocytes of mice in the model group. Significant increases were observed in serum levels of TC, TG, LDL, ALT, AST, TNF-α, IL-1β, and IL-6 in mice, while HDL levels were significantly reduced. Liver tissue exhibited significantly elevated levels of TC and TG, along with markedly increased relative expression levels of RIP3 and p-MLKL proteins. Additionally, the relative expression levels of RIP3 and MLKL mRNA were significantly elevated. Compared with the model group, mice in each Suaeda salsa polysaccharide intervention group exhibited reduced body weight and decreased liver index; the degree of pathological liver damage in mice was significantly improved. Liver lipid droplet area and size decreased in mice from the low, medium, and high-dose Suaeda salsa polysaccharide intervention groups. Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-alpha, interleukin-1β, and interleukin-6 were markedly decreased, whereas high-density lipoprotein levels showed a significant increase. Liver tissue TC and TG levels were significantly reduced, while the relative expression levels of RIP3 and p-MLKL proteins were markedly decreased. The relative expression levels of RIP3 and MLKL mRNA were significantly reduced. Conclusion Suaeda salsa polysaccharide significantly reduces liver damage induced by a high-fat diet. It may alleviate the onset and progression of metabolic-associated fatty liver disease by regulating the release of inflammatory mediators and reducing hepatic programmed necrosis.