Objective To investigate the mechanism of Xiangsha Liujunzi decoction in reducing hepatic lipid deposition in rats with spleen-deficiency and hyperlipidemia based on cuproptosis.Methods Eighteen healthy Sprague Dawley(SD)rats were randomly divided into normal,spleen-deficiency and hyperlipidemia,and traditional Chinese medicine(TCM)groups.Rats in the spleen-deficiency and hyperlipidemia group and TCM group were subjected to exhaustive swimming combined with a high-fat diet,while the normal group was fed an ordinary diet.After 12 weeks of modeling,rats in the TCM group were gavaged with Xiangsha Liujunzi decoction(11.34 g·kg-1),and the other two groups were gavaged with 0.9%sodium chloride solution in corresponding volume.After 4 weeks of intervention,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and liver lipid levels were measured.The mRNA expression levels related to cuproptosis were monitored using a PCR Array.Results Compared with levels in the normal group,the serum levels of TC,TG,and LDL-C in the spleen-deficiency and hyperlipidemia group were increased(P<0.01),while HDL-C was decreased(P<0.01).Compared with the spleen-deficiency and hyperlipidemia group,the TCM group showed decreased TC,TG,and LDL-C content(P<0.01),increased HDL-C content(P<0.01),and reduced lipid deposition in the liver.11 dif-ferentially expressed genes related to cuproptosis were detected using a PCR Array assay.Seven differentially expressed genes related to cuproptosis were found in the livers of the spleen-deficiency and hyperlipidemia group compared to those in the normal group;meanwhile,six differentially expressed genes were found in the TCM group compared with those in the spleen-deficiency and hyperlipidemia group.Five codifferentially expressed genes were identified among the abovementioned genes.Furthermore,three differentially expressed genes were found between the two paired comparison groups(≥1 fold or≤1 fold),and then Dldand Glswere screened out,which could reg-ulate mitochondrial cuproptosis.The expression levels of Dldand Glswere verified by qPCR,which were consistent with our PCR Array.Conclusion Abnormal expression of Dld and Gls related to cuproptosis in the liver may be a potential mechanism of abnormal lipid metabolism,and may be an important target of Xuanxiangsha Liujunzi decoction in the treatment of spleen-deficiency and hyperlipidemia.