Based On NF-?B Pathway, The Anti-atherosclerotic Mechanism And Dyslipidemia Syndrome Of Tiaozhi Tongmai Granule Were Studied

Objective1.By observing the effect of the expression of proteins caused by remnant-like particle cholesterol(RLP-C)with rich Triglyceride in apoE-/-mice,such as Aortic arch plaque,aortic arch adhesion molecule-1(ICAM-1),vascular cell adhesion molecule(VCAM-1)and nuclear factor-kappa B(NF-?B).To explore the mechanism by which RLP-C interferes with the expression of ICAM-1 and VCAM-1 through the classical pathway of NF-?B,and the effect of lipid regulating and blood improving Granules intervention.2.Through clinical cross-sectional investigation and research methods,analysing distribution characteristic of many indicators in patients with various syndrome of dyslipidemiag,such as total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and High-density lipoprotein cholesterol(HDL-C),RLP-C,ICAM-1,as well as VCAM-1,Combining macroscopic diagnosis of Chinese medicine with the microscopic indications of modern medicine,we sought to find out the relationship between physical indicators and characteristics of syndromes,with a view to exploring new ideas for early treatment of dyslipidemia,as well as for prevention and treatment of AS with traditional Chinese medicine.Methods1.In animal experiments,30 pieces of 6-week-old ApoE-/-mice were randomly divided into model group,fenofibrate group,and lipid regulating&blood improving group,10 pieces in each group,and another 10 pieces of 6-week-old C57BL/6J mice were selected for reference.As a normal reference group.The mice were risen with common feed daily,and the model group was fed daily with high-fat feeding.The medicine given group was fed daily with high-fat feeding and Lipid regulating&blood improving Granules or fenofibrate.After 12 weeks of feeding,serum levels of TC,TG,LDL-C and RLP-C are measured by biochemical assay.ICAM-1 and VCAM-1 levels are detected by ELISA.Morphological changes of the aortic arch are observed by HE staining;The expression of ICAM-1 and VCAM-1 in aortic arch are observed by Immunohistochemistry.The expressiones of ICAM-1,VCAM-1,NF-?B,p-NF-?B,I?B? and p-I?B? protein in aortic arch are detected by Western blot.2.In clinical studies,data of primary dyslipidemia patients who were admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine and Aerospace Central Hospital from May 2016 to December 2016 were selected.According to the corresponding inclusion and exclusion criteria for the collection of cases,we have acquired general information of patients,then have filled in the observation form of syndrome cases of traditional Chinese medicine science,and have taken patient's morning fasting venous blood for detection TC,TG,LDL-C,HDL-C,RLP-C VCAM-land ICAM-1,in the meantime 20 healthy personshave been screened for comparison.Finally,we have statistically analyzed the collected data.ResultAnimal experiment1.Blood lipid test results in mice showed that the levels of TC,LDL-C,and RLP-C in the model group were significantly higher than those in the normal control group,and compared with the model group,Serum TG,RLP-C levels of fenofibrate group and Lipid regulation&Blood improving Granule group were significantly reduced.2.The results of mice's adhesion molecules showed that the levels of ICAM-1 and VCAM-1 in the model group were significantly higher than those in the normal group,while those in the Fenofibrate group and Lipid regulating&blood improving Granule group were significantly less than those in the model group.3.HE staining of mice's aortic arch showed that the aortic intima was smooth and no inflammatory cell infiltration was observed in normal control mice.In the model group,there was obvious plaque formation in the aorta of the mice,and the lumen was narrow.There were a lot of cholesterol crystals and infiltration of inflammatory cells inside the plaque.Follicular formation was also observed in fenofibrate group and Lipid regulating&blood improving group,but the inflammatory cell infiltration in the plaque was reduced compared with the model group.4.The results of immunohistochemistry showed that no ICAM-1 and VCAM-1 particles were observed under the endothelium in the aortic arch of normal control mice.A large number of those particles were observed under the endothelium in the mouse aortic arch of the model group.In fenofibrate group and lipid regulating&blood improving group,ICAM-1 and VCAM-1 particles were decreased compared with the model group,mainly locate in the subendothelial plaques.5.Western blot results showed that compared with normal control group,the expression of ICAM-1,VCAM-1,p-NF-?B,and p-I?B? protein in the model group were significantly higher,but compared with the model group,The expression of VCAM-1,p-NF-?B and p-I?B? protein in the aorta of benobeite group and Lipid regulating&blood improving Granule group were significantly decreased;while the expression of ICAM-1 in the aorta of the two above mentioned group was lower than that of the model group.no statistical significance is found.Clinical study1.Clinical Studies have found that the distribution ratio of syndrome types of Traditional Chinese Medicine Science from high to low is:Turbid Phlegm repression syndrome(24.6%)>Syndrome of qi stagnation and blood stasis(23.9%)>spleen and kidney yang deficiency(21.0%)>liver and kidney Yin deficiency syndrome(18.1%)>yin deficiency and yang hyperactivity(12.3%).2.The characteristics of blood lipids in patients with different syndrome types of dyslipidemia are compared with those of normal control group,which indicates that levels of TG and LDL-C of turbid phlegm group,spleen and kidney yang deficiency group,liver and kidney yin deficiency group,yin deficiency&yang hyperactivity group and qi stagnation&blood stasis group have increased significantly while the level of HDL-C have decreased significantly.Among them,TG level of the turbid phlegm group is significantly higher than that of the liver-kidney yin deficiency group,and the yin deficiency-yang hyperactivity group.And the qi stagnation&blood stasis group is significantly higher than that of the liver-kidney yin deficiency group.3.The characteristics of RLP-C in patients with different syndrome types of dyslipidemia are in the following:compared with the normal control group,The level of RLP-C turbid phlegm group,spleen and kidney yang deficiency group,liver and kidney yin deficiency group,Yin deficiency&Yang hyperactivity group,and qi stagnation&blood stasis group were significantly increased;among them,the level of RLP-C of the turbid phlegm group was the highest,and the level of RLP-C was significantly higher than those of the spleen-kidney yang deficiency group,the liver-kidney yin deficiency group,Yin deficiency&Yang hyperactivity group.In addition,RLP-C level of the qi stagnation&blood stasis group is significantly higher than that of the liver-kidney yin deficiency group.4.The characteristics of adhesion molecules in patients with different syndrome types of dyslipidemia are in the following:compared with the normal control group,the levels of ICAM-1 and VCAM-1 in the turbid phlegm repression group increased significantly;while much lower than those of the turbid phlegm repression group,the spleen and kidney yang deficiency group,liver and kidney yin deficiency group,Yin deficiency&Yang Hyperactivity group and Qi stagnation&blood stasis group.The levels of VCAM-1 are significantly decreased in spleen and kidney yang deficiency group,liver and kidney yin deficiency group and Yin deficiency&Yang Hyperactivity group.5.Serum RLP-C is positively correlated with TC,TG,ICAM-1 and VCAM-1,while negatively correlated with HDL-C.Conclusions1.RLP-C may increase the expression of ICAM-1 and VCAM-1 and attribute to pathological changes of AS by activating NF-?B,hence reduce the level of RLP-C,inhibit NF-?B pathway,reduce the expression of ICAM-1 and VCAM-1,and delays AS lesions with Lipid regulating and blood improving granules.It is suggested that Lipid regulating and blood improving granules can control the metabolism of blood lipids,inhibit inflammatory reaction,and reduce the damage of the endothelium.with a clear effect of stabilizing plaque,improving lesions,and preventing AS.2.Patients with dyslipidemia are most frequently seen with symdromes of turbid phlegm repression,qi stagnation&Blood stasis,and spleen-kidney yang deficiency.Serum TG,RLP-C,ICAM-1,and VCAM-1 levels are closely related to turbid phlegm syndromes,and TG,RLP-C,ICAM-1,and VCAM-1 may be considered as one of the microscopic indicators of turbid phlegm repression.Because of the predictive value of RLP-C for cardiovascular disease,it is suggested that patients with dyslipidemia may be more prone to cardiovascular disease.If the principle of treatment according to syndrome differentiation is followed in clinical practice,rational use of Chinese medicine treatment may enable patients with dyslipidemia to obtain greater benefits.