Effect Of Tripterine On The Sirt7/NF-?b Pathway In Atherosclerotic Plaques Of High Homocysteine ApoE^-/-Mice

Background Homocysteine?Hcy?,as one of the independent risk factors of cardiovascular disease,aggravates the damage of inflammation and oxidative stress,leading to the formation of atherosclerotic plaques.The inflammatory response was accompanied by activation of the NF-?b pathway and increased downstream Caspase-1 expression.Oxidative stress injury is mediated by NOX-4,and the activation of NF-?b pathway is synergistically involved.Sirt7is involved in the intruclear shuttling of NF-?b pathway P-p65 and is closely related to the activation of NF-?b pathway,but the relationship between the two in the course of atherosclerotic plaque formation remains unclear.Tripterine has anti-inflammatory and anti-oxidant effects and inhibits the activation of NF-?b pathway,but it is not clear whether Sirt7 is involved.Objective To study the effects of tripterine on inflammation and oxidative stress damage in atherosclerotic plaques of ApoE^-/-mice with hyperhomocysteinemia,and to explore the mechanism of tripterine's anti-atherosclerosis.Methods 42 healthy male ApoE-/-mice were 7 weeks old,3 to 4 in each cage,at room temperature?22?±1??,with appropriate humidity,free drinking water,and adaptive feeding for 1 week.which were divided into control group?general diet?,high-methionine treatment group?4.4%methionine diet?,and treatment group?4.4%methionine diet+tripterine?1mg/Kg/day drinking water intake??.The reliability of the hyperhomocysteine model was confirmed by weight measurement and serum biochemical detection of Hcy level;The progression of atherosclerotic plaques in ApoE-/-mice on the high-methionine diet was determined by oil red O staining and HE staining,and the inhibition degree of tripterine on the formation of atherosclerotic plaques was determined.Immunohisto-chemistry was used to detect the expression sites and levels of proteins of Sirt7/NF-?b pathway and proteins associated with inflammation and oxidative stress.Results 1.Compared with the control group,the serum homocysteine level of the hypermethionine group and the treatment group increased significantly,and the average body weight decreased.2.The plaque area of the high-methionine group was significantly larger than that of the control group,the expression level of related Sirt7/NF-?b pathway proteins?Sirt7,P-p65?was increased,and the expression level of inflammatory and oxidative stress related proteins?Caspase-1,NOX-4?was increased.3.The plaque area of the group treated with tripterine was significantly lesser than that of the group with higher methionine,the expression level of related Sirt7/NF-?b pathway proteins?Sirt7,P-p65?decreased,and the expression level of inflammatory and oxidative stress related proteins?Caspase-1,NOX-4?decreased.Conclusion 1.High-methionine diet induced hyperhomocysteinemia in ApoE^-/-mice,activated the Sirt7/NF-?b signaling pathway,aggravated inflammation and oxidative stress damage,and accelerated the formation of atherosclerotic plaques.2.Tripterine inhibits the activation of Sirt7/NF-?b signaling pathway in atherosclerotic plaque,reduces inflammation and oxidative stress damage,and delays the formation of atherosclerotic plaque.