基于肝组织代谢组学探讨左金丸改善肝纤维化潜在机制OA

Objective:This study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis.Methods:Twenty-four mice were randomly allocated into normal group,model group,positive drug group(silymarin,100 mg·kg-1),and Zuojinwan group(Zuojinwan solution,2.5 g·kg-1),with per group six mice.Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10％carbon tetrachloride(CCl4)(0.5 μL·g-1,three times weekly for 8 weeks)in all groups except the normal group.During the final 4 weeks,the silymarin group received silymarin(100 mg·kg-1)by gavage thrice weekly,while the Zuojinwan group was administered Zuojinwan solution(2.5 g·kg-1)under the same regimen.After the last administration,the levels of liver fibrosis indicators and liver injury markers in serum were detected.The pathological morphological changes of the liver tissues were observed.The levels of liver fibrosis markersα-smooth muscle actin(α-SMA)and Collagen Ⅰ(Col Ⅰ)were detected.Metabolomics was analyzed on mice's liver tissues.The mice's serum was collected for metabolomics analysis.Results:Compared with the model group,Zuojinwan significantly improved indicators related to liver fibrosis and liver injury.Compared with the normal group,the model group showed significantly elevated levels of fibrosis markers such as laminin(LN),hyaluronic acid(HA),procollagen type Ⅲ(PC-Ⅲ),and type Ⅳ Collagen(Ⅳ-C),while liver injury indicators such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),lactate dehydrogenase(LDH),and total bilirubin(TBIL),exhibited a marked upward trend(P＜0.05).Compared with the model group,the silymarin group showed a significant decrease in the aforementioned indicators(P＜0.05).Notably,compared with the model group,the Zuojinwan group exhibited a significant reduction in all these indicators(P＜0.05),with efficacy comparable to that of the silymarin group.Zuojinwan reduced mRNA and protein levels ofα-SMA and Col Ⅰ in the liver tissue.Metabolomics results revealed that compared with the model group,Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1,6-bisphosphate(FBP),nicotinamide adenine dinucleotide phosphate(NADPH),sodium beta-D-fructose 6-phosphate(F6P),dihydroxyacetone phosphate(DHAP),fumaric acid,and D-glucose 6-phosphate(G6P)(P＜0.05).Serum enzyme-linked immunosorbent assay(ELISA)was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism.Conclusion:These results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.