Exploration on the mechanism of Ruanjian Qingmai Granules on the treatment of arteriosclerosis obliterans based on network pharmacology and experimental validation
Objective:To explore the potential therapeutic targets and mechanism of Ruanjian Qingmai Granules(RJQM)on the treatment of arteriosclerosis obliterans(ASO)by using network pharmacology techniques,and further validated using ApoE-/-mice.Methods:Various databases were used to analyze the intersectional targets of RJQM action on ASO,and GO and KEGG signaling pathway analysis was performed.A total of 30 ApoE-/-mice were given a high-fat diet,and randomly divided into model group,RJQM low-dose group(RJQM-L),RJQM medium-dose group(RJQM-M),RJQM high-dose group(RJQM-H),and positive control group,6 mice in each group,C57BU6J mice of the same weekly age were used as control group.These mice were gavaged continuously for 18 weeks.The serum levels of TC,TG,LDL-C and HDL-C were measured.The morphological changes of liver tissue and aortic arch were detected by HE staining.The lipid deposition in intact arteries of mice was detected by oil red ostaining.And the mRNA expression of ABCA1,ABCG5,and ABCG8 genes related to cholesterol metabolism was detected by qRT-PCR.Results:KEGG pathway enrichment analysis revealed that RJQM may play a therapeutic role by regulating lipid metabolism signaling pathway.Compared with the model group,the TG level was reduced in the RJQM-H group(P<0.05),the swelling of liver cells and fat vacuolation pattern in mice treated with three dose RJQM groups were improved,the area of atheromatous plaque in the aortic arch significantly reduced(P<0.01),and the area of oil-red coloring lipid droplets significantly reduced(P<0.05),the expression of ABCA1 and ABCG5 mRNA was significantly up-regulated in the RJQM-H group(P<0.01),and the expression of ABCG8 mRNA in three dose RJQM groups was down-regulated(P<0.01).Conclusions:RJQM can regulate lipid and atherosclerotic signaling pathways and exert an intervention in ASO.