The Correlation Between NF-kB Pathway And Inflammation, Apoptosis And Autophagy In Atherosclerosis

Objective: To investigate the association of high-fat diet with NF-k B pathway,inflammation,apoptosis and autophagy in atherosclerosis and study the effects and mechanisms of targeted intervention on NF-k B signaling pathway on atherosclerosis.Methods: Eighty Apo E-/-male mice were randomly divided into normal diet group and high-fat diet group.High-fat diet mice were divided into control group(n=20),recombinant adeno-associated virus serotype 9(r AAV9)-e GFP group(n=20)and r AAV9-inhibitor protein of κB(IκB)α group(n=20).Obtain specimens after feeding to different ages.The expressions of blood lipid,lipid plaque,oxidative stress,apoptotic protein,NF-k B signaling pathway protein and autophagy protein were detected.Results:1)Compared with ordinary diet mice,blood lipid levels in high-fat diet mice increased significantly(P<0.05).P-p65 was up-regulated(P<0.05),IκBα was down-regulated(P<0.05).The levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 8(IL-8)were higher in high-fat diet mice(P<0.05).In addition,the high fat diet mice had increased Bcl-2/Bax and microtubule-associated protein 1A/1B-light chain 3(LC3)Ⅱ/LC3Ⅰ(P<0.05),up-regulated p-p65(P<0.05),down-regulated p62 and IκBα(P<0.05).The area of arterial plaque increased(P<0.05)in the high fat diet mice.2)After treatment with r AAV9-IκBα,IκBα up-regulated in high-fat diet mice(P<0.05).In addtion,p-p65 and TNF-α were decreased after injection(P<0.05).The injection of r AAV9-IκBαincreased the level of endothelial nitric oxide synthase(e NOS)(P<0.05)and up-regulated the expressions of Bcl-2/Bax,p62,LC3Ⅰ and LC3Ⅱ(P<0.05).Conclusion: High-fat diet can participate in the formation of atherosclerosis by activating NF-k B pathway and inflammation,promoting apoptosis and autophagy.The inhibition of NF-k B pathway candown-regulate the expression of inflammation,apoptosis and autophagy,and reduce atherosclerotic lesions.