Based On I?B?/NF-?B Signaling Pathway To Explore The Mechanism Of Wenxiao Recipe Intervention In Atherosclerosis

Objective:By observing the histopathological changes,serum biochemical indexes and the expression levels of I-kappa B alpha and NF-kappa B protein in AS model rabbits,the mechanism of Wenxiao recipe in preventing and treating AS was explored.Method:Thirty-eight clean-grade experimental rabbits.Thirty-eight rabbits were randomly divided into model group?29 rabbits?and blank group?9 rabbits?.Blood samples were collected from the ear vein of experimental rabbits.Serum lipid indexes?TG,TC,LDL-C,HDL-C?,liver function indexes?AST,ALT?,renal function indexes?Cr,BUN,UA?and creatine kinase?CK?were measured and weighed.The AS model was made by feeding a high fat diet.After 12 weeks,2 rabbits were randomly selected from the model group to observe the model and weigh them.The above serum indicators were also measured.After the successful establishment of the model,the model group was separated into Wenxiao recipe group,simvastatin group and model group.The high fat diet was stopped and the standard diet was used for feeding,and the drug intervention was carried out.The model group was given normal saline daily according to the dosage of 10 ml·kg^-1;the Wenxiao recipe group was given free Decoction granules daily,the dosage was 383.33 mg·kg^-1of Pinellia ternate,575mg·kg^-1of danpi,tulip,Salvia metrorrhagia,leech and earthworm respectively;the simvastatin group was given simvastatin tablets daily at the dosage of 0.77 mg·kg^-1,weighed after 8 weeks,and the above serum indexes were measured.The abdominal aorta was taken for anesthesia.The expression of I kappa B alpha protein and NF-kappa B protein were detected by immunohistochemistry and Western blot.Result:1.Morphological Observation of Pathological TissuesAfter 12 weeks of feeding with a high-fat diet,two rats were killed randomly in the model group.The abdominal aorta was taken and the medial wall of the blood vessel was expanded.A large number of milky white atherosclerotic plaques were observed on the medial wall of the blood vessel with naked eyes.Hematoxylin-eosin?HE?staining showed that the nucleus was blue-stained and the cytoplasm was pink or red.Under 100x light microscope,endothelial cells proliferated and intima thickened.Under 200*light microscope,lipid accumulation,foam cell accumulation,irregular smooth muscle cell arrangement,atherosclerotic plaque formation on the vascular wall,and successful modeling.2.Observation of TC,TG,HDL-C and LDL-C levelsAfter 12 weeks,compared with the blank group,HDL-C level decreased significantly and serum TG,TC and LDL-C levels increased significantly?P<0.01?.The model group was randomly divided into model group,Wenxiao recipe group and simvastatin group.There was no significant difference in blood lipid index?TG,TC,LDL-C,HDL-C?levels among the three groups before intervention?P>0.05?.After 8 weeks of drug intervention,the blood lipid index between the Wenxiao recipe group,the simvastatin group and the model group was higher,the HDL level was increased,and the serum levels of TC and LDL were significantly decreased?P<0.01?,and TG level decreased?P<0.05?.There were no significant differences in blood lipids?TG,TC,LDL-C,HDL-C?between the Wenxiao recipe group and the simvastatin group?P>0.05?.3.Observation of ALT,AST,Cr,UA,BUN and CK levelsAfter 12 weeks,compared with the blank group,the levels of liver function index?ALT,AST?,renal function index?Cr,UA,BUN?and creatine kinase?CK?in the model group increased significantly?P<0.05?.Before intervention,there were no differences in liver function index?AST,ALT?,renal function index?Cr,UA,BUN?and creatine kinase?CK?After 8 weeks of drug intervention,the liver function index?ALT,AST?and renal function index?Cr,UA,BUN?decreased compared with the model group?P<0.01?,and there was no significant difference in creatine kinase level?P>0.05?.There were no significant differences in liver function indexes?ALT,AST?and creatine kinase?CK?between the simvastatin group and the model group?P>0.05?,and renal function indexes?Cr,UA,BUN?were decreased?P<0.01?.There were no statistically significant differences in the levels of liver function?ALT,AST?,renal function?Cr,UA,BUN?and creatine kinase?CK?between the Wenxiao Recipe group and the simvastatin group?P>0.05?.4.Effect of Wenxiao Recipe on the Expression of I kappa B alpha and NF-kappa B ProteinImmunohistochemical and Western blotting results showed that the expression of I kappa B alpha and NF-kappa B in the model group was higher than that in the blank group,the difference was statistically significant?P<0.01?.Compared with the model group,Wenxiao recipe group could significantly increase the expression of I kappa B alpha?P<0.01?and inhibit the expression of NF-kappa B?P<0.01?.Conclusion:1.Wenxiao recipe can reduce the levels of TC,LDL and TG,and improve the metabolism of blood lipids.2.Wenxiao recipe can increase the level of I kappa B alpha protein,inhibit the activation of NF-kappa B and reduce the over expression of pro-inflammatory genes,which have a certain role in stabilizing plaque.3.Wenxiao recipe had no significant adverse effects on liver function indicators?AST,ALT?,renal function indicators?Cr,UA,BUN?and creatine kinase levels.