Based On The TLR4/MyD88/NF-?B Pathway To Explore The Intervention Mechanism Of Huayu Qutan Fang On The Aortic Inflammatory Injury In AS Rabbits

Purpose:By establishing rabbit atherosclerosis model,observe the intervention effect of Huayu Qutan Fang on AS rabbits,to discuss the mechanism of Huayu Qutan Fang on anti-atherosclerosis.Material and method:After 2 weeks of adaptive feeding,,Ninety healthy male New Zealand white rabbits were randomly divided into normal control group,model group,simvastatin group,low dose group of Huayu Qutan recipe,middle dose group of Huayu Qutan recipe and high dose group of Huayu Qutan recipe.There are 15 rats in each group.The normal control group was fed with normal diet and normal saline(250mg.kg-1)was injected intravenously into the ear margin,while the other groups were fed with high fat diet and bovine serum albumin saline solution(250mg.kg-1)intravenously.After eight weeks,the low dose group of Huayu Qutan recipe,the middle dose group of Huayu Qutan recipe,the high dose group of Huayu Qutan recipe and simvastatin group were given the corresponding drug intervention respectively.In the high dose group,the dosage was 4,8,16 g.kg-1.d-1),(simvastatin was 1.5%.4 mg.kg-1);In the normal control group,the model group was given the same volume of saline(8 ml.kg-1.d-1)once a day for 4 weeks.After 12 weeks,the serum lipid level of rabbits in each group was measured by automatic biochemical analyzer.The changes of aortic morphology and plaque deposition in each group were observed by he staining,and the levels of serum inflammatory indexes TNF-?,IL-1? in each group were detected by ELISA method.The expression of TLR4?MYD88?TRIF?IRAK4?TRAF6?TAK1?IKK??NF-kB P65 and other proteins in aortic was detected by Western Blot.Results:1.Blood lipid levels showed,compared with the normal control group,Serum TC,TG and LDL-C levels in the model group were significantly higher than those in the normal control group(P<0.01),HDL-C levels were significantly lower(P<0.01);compared with he model group,TC,LDL-C and TG levels in the low,medium and high dose groups of Huayu Qutan Fang and simvastatin group were significantly lower(P<0.01),and HDL-C levels were significantly higher(P<0.01).2.HE staining showed,compared with the normal control group,model group have a large number of foam cells aggregation and plaque formation in the aorta.Compared with the model group,the distribution of foam cells and plaques in different drug intervention groups varied in varying degrees.3.The results of serum ELISA test showed that the levels of IL-1??TNF-? in the model group were significantly higher than those in the normal control group(P<0.01).Compared with the model group,the levels of IL-1? and TNF-? in the low,medium and high dose groups of Huayu Qutan Fang and simvastatin group were significantly lower(P<0.05 or P<0.01).Western Blot's detection of aorta protein's expression quantit.Compared with the control group,the expression levels of TLR4,MYD88,TRIF,IRAK4,TRAF6,TAK1,IKK? and NF-kB P65 protein in the aorta of rabbits in the model group were significantly higher(P<0.01);compared with the model group,the expression levels of TLR4,MYD88,TRIF,IRAK4,TRAF6,TAK1,IKK? and NF-kB P65 protein in the aorta of rabbits in the drug intervention groups were improved in varying degrees,among which the high dose group of Huayu Qutan Fang and simvastatin group were used.(P<0.05 or P<0.01)the effect was more significant.Conclusion:1.Huayu Qutan Decoction can effectively improve blood lipid level and atherosclerotic plaque formation in atherosclerotic rabbits,and can effectively prevent and treat atherosclerosis.2.The mechanism of Huayu Qutan Decoction on aortic injury in atherosclerotic rabbits may be related to inhibiting TLR4/My D88/NF-kB signaling pathway and influencing related inflammatory factors.