Effects Of Jingmai Quban Granules On Carotid Plaque And Expression Of MMP-9 And TIMP-1 In Mice Model With Phlegm And Blood Stasis Syndrome

Objective:Through network pharmacology,the core targets and metabolic pathways of Jingmai Quban Granules in the treatment of CAS plaque were explored,and the potential mechanism of its participation in inflammatory response was predicted.The effects of different concentrations of Jingmai Quban Granules on the expression of related indexes in mice with phlegm and blood stasis type CAS plaque were verified by animal experiments,which provided experimental data for the clinical application of this prescription in the future.Methods:1.Network pharmacology:The main compound components of the core prescription of Jingmai Quban Granules were retrieved from the database to obtain the intersection target with CAS plaque,and the Jingmai Quban Granules-components-targets network were constructed for GO and KEGG analysis.2.Animal experiment:CAS plaque model was established by high-fat,high-sugar,high-salt diet combined with humid environment in Apo E^-/-mice,and 5 mice were selected as control.After 12 weeks,3 rats were randomly selected for HE staining and oil red O staining to test the modeling.The model rats were randomly divided into western medicine group,Jingmai Quban Granule high,medium and low three groups and blank model group five groups,then intragastric administration for 4 weeks.After treatment,abdominal aorta blood and carotid artery dissection were performed.The pathological changes of the tissues were observed under light microscope.Serum lipid,blood glucose,MMP-9 and TIMP-1 levels were determined by ELISA.Results:1.Network pharmacology:The core prescription of Jingmai Quban Granules contains292 active ingredients and 784 potential targets.Through screening,175 common targets were obtained,and 68 core proteins were screened.The main active ingredients were quercetin,aloe-emodin etc.There were 18,572 main biological processes and 160 related signaling pathways involved AGE-RAGE,fluid shear stress and atherosclerosis etc.2.Animal experiment:Before modeling（6W）,after modeling（18W）and after intragastric administration（22W）were three observation nodes.（1）Morphological changes in mice:In contrast to the normal diet group,the model group showed morphological changes such as obesity and drowsiness,changes in hair luster,and laziness,suggesting that the model was successful.After intragastric administration,compared with the blank model group,the symptom relief degree of the three dose group and the western drug group was better than blank model group.（2）Changes of body weight,body length and Lee’s index:There was no significant difference in body length,body weight and Lee’s index between the 6W groups（P>0.05）.The difference of body weight and Lee’s index among 18W groups was statistically significant（P<0.05）.The body weight of the model group was obviously higher than that of blank group,and the comparison between the groups was statistically significant（P<0.01）.（3）Changes in blood levels:After 18W,LDL-C,TC,TG and blood glucose levels in the model group were significantly higher than those in the blank group,while HDL-C was lower than that in the blank group,with statistical significance（P<0.01）.After 22W,the levels of TC,TG and LDL-C in the high-dose group were significantly lower than those in the low-dose group（P<0.05）.MMP-9:Blank group was lower than model group,the difference was statistically significant（P<0.01）,and high dose group was significantly different from model group（P<0.01）.TIMP-1:Compared with model group,high-dose group had significant difference（P<0.01）.Compared with blank group,low dose group had significant difference（P<0.05）.（4）Pathological results:HE staining results:No abnormality was found in the carotid artery of mice in blank group,the tube wall was smooth,and no lipid deposition was observed.In the model group,irregular ring changes were observed,a large number of foam cells gathered,and surface fiber caps were formed.The model group was the most significant,and the high,medium and low dose groups and the western medicine group had a certain degree of relief.Oil red O staining results:T The plaque formation was the most serious in the model group.Compared with the model group,the high,medium and low dose groups of Jingmai Quban Granules had different therapeutic effects on carotid plaque,and the high dose group had the best effect,and the difference was statistically significant（P<0.01）.Conclusion:1.Jingmai Quban Granules in the treatment of CAS plaques can play a role through a variety of active ingredients and targets,and participate in the formation of AS by affecting cellular inflammatory factors to achieve therapeutic effects.2.Jingmaiquban granules can regulate the level of inflammatory indicators by mediating intracellular inflammatory response,and play a role in the treatment of carotid atherosclerotic plaques;3.Compared with simvastatin,the middle and high dose groups of Jingmai Quban Granules can effectively improve CAS plaque,reduce blood lipid and blood glucose（P<0.01）.