Study on the Lipid-Regulating Mechanism of Zexie Decoction on Hyperlipidemia Model Mice Based on the miR21/PI3K-Akt/SREBP Pathway

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.

METHODS ELISA method was used to detect the four blood lipid indexes, liver function indicators and cholesterol acyltransferase levels in serum. HE and Oil Red O staining were used to determine the pathology of liver tissue. Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction, and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized. PCR chip technology was used to detect the target genes for network pharmacology screening, and qPCR and Western blot were used to detect gene and protein expression levels.

RESULTS Zexie Decoction significantly regulated the four blood lipid indexes in hyperlipidemia model mice, improved the increase in liver damage indicators caused by high lipids, and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue. HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue, reduced lipid deposition in liver tissue, and significantly decreased the positive area ratio (P < 0.01). The PCR chip obtained 44 reverse-regulated genes, GO functional enrichment analysis obtained 266 entries, and KEGG pathway enrichment analysis screened 99 signaling pathways. The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG, AKT1, and IL-6 genes (P < 0.05, P < 0.01), upregulated the expression of ABCG1 gene (P < 0.05), downregulated PI3Kinase p110β, p-AKT (Ser473) and SREBP-1c protein expression levels (P < 0.01), and reversely regulated miR21-5p (P < 0.01).

CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia. Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body, and is closely linked to the miR21/PI3K-Akt/SREBP pathway. The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.