| Objective:1.To observe the effect of safflower yellow for inj ection on blood lipid levels in hyperlipidemia model mice.2.The key targets and possible mechanisms of safflower yellow for inj ection in the treatment of hyperlipidemia were screened out by network pharmacology.3.Based on network pharmacology analysis,the expression of key proteins in the PPAR signaling pathway was detected,and the potential mechanism of safflower yellow for injection in the treatment of hyperlipidemia was explored.Method:1.Select 70 SPF mice,fed with basal diet,normal drinking water and free food,and randomly divided into blank group(15 mice)and high-fat group(5 5 mice).The blank group was given the same volume of normal saline every day.The lipid group was fed with lipid emulsion to replicate the animal model of hyperlipidemia.After 3 weeks,the blood lipid levels of the animals were detected to confirm that the hyperlipidemia model was successfully established and used in this experimental study.The animals in the blank group were used as the blank control group in this study.After successful modeling,animals were randomly assigned to model group,fenofibrate group(26 mg/kg),high-dose safflower yellow for inj ection group(26 mg/kg),and low safflower yellow for inj ection according to body weight.The dose group(13 mg/kg),12 mice in each group,were fed with common feed.The model group and each administration group were given high-fat emulsion gavage to continue modeling.Intraperitoneal inj ection of water or corresponding drugs for 21 consecutive days,once a day.The food intake of the mice was recorded every day,and the body weight of the mice was measured every week.2 hours after the last administration,blood was collected under anesthesia,the serum was separated,and the blood lipid indexes and oxidation indexes of each group were detected;the liver was separated,weighed,and the liver index was calculated;HE The pathological changes of liver tissue were observed by staining.2.Conduct network pharmacology analysis based on the above experimental research.The target of the active ingredient is obtained through the drug database.Search disease databases to collect disease targets for hyperlipidemia.Using the Venny platform to intersect disease targets and component targets,potential therapeutic targets for the treatment of hyperlipidemia with safflower yellow for injection were obtained.A protein interaction network(PPI)was constructed for the obtained intersection targets to analyze the protein interaction relationship;GO function and KEGG pathway enrichment analysis were performed.3.ELISA was used to determine the levels of lipid metabolism-related enzymes and proteins affecting related enzymes,and 4 important gene targets in CHO metabolism were selected,and the proteins existing in the PPAR signaling pathway were detected by Western Blot(WB):PPARγ,LXRα,CYP7A1,ABCA1,etc.Result:1.Safflower yellow for inj ection can reduce CHO and LDL-C(P<0.01,P<0.05);the contents of SOD and GSH-px in the liver tissue of mice in the low-dose group were significantly increased(P<0.05),and the content of MDA was significantly increased(P<0.05).Significantly decreased(P<0.05),and HE staining of liver histopathology showed that safflower yellow for inj ection could alleviate fatty degeneration of liver tissue cells.2.Network pharmacology study of safflower yellow for injection in the treatment of hyperlipidemia:The study found that there are 52 common targets of hydroxysafflor yellow A and hyperlipidemia.The GO and KEGG enrichment analysis found that the key targets of safflower yellow for injection in the treatment of hyperlipidemia were enriched in signaling pathways such as PPAR,thyroid hormone,fluid shear stress and atherosclerosis.3.The study of safflower yellow for injection on lipid synthesis and metabolism in hyperlipidemia model mice found that it could inhibit the activity of HMG-CoA reductase,and LCAT,CYP7A1,and PPARγ all increased(P<0.05);,HL content did not change significantly.WB results showed that the protein expressions of PPARγ,LXRα,ABCA1,and CYP7A1 in the model group were significantly decreased(P<0.05),and the protein expressions of PPARγ,LXRα,ABCA1,and CYP7A1 in each administration group were significantly increased(P<0.05).Conclusion:1.Safflower yellow for injection has a hypolipidemic effect on lipid emulsion-induced hyperlipidemia mice,can reduce oxidative stress and lipid peroxidation damage,and inhibit the accumulation of fat in liver cells.2.The network pharmacology method was used to analyze that safflower yellow for injection can treat hyperlipidemia through multiple targets and multiple mechanisms of action,and its lipid-lowering mechanism may be related to PPAR signaling,thyroid hormone,fluid shear stress and Atherosclerosis and other pathways.3.Safflower yellow for inj ection can activate the PPARγ-LXRα-ABCA1/C YP7A1 signaling pathway,promote cholesterol metabolism,and regulate lipid disorders. |
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