Sinomenine inhibits atherosclerosis progression in mice by activating nuclear factor E2 related fac-tor 2 pathway
Objective To investigate the effect of sinomenine on atherosclerosis in apolipoprotein E gene knockout(ApoE-/-)mice and its mechanism.Methods Using a random number table method,male ApoE-/-mice aged 6-8 weeks were divided into model group(n=10),low-dose sinomenine group(n=10)and high-dose sinomenine group(n=10).A total of 30 mice were fed with high-fat diet for 16 weeks.After 8 weeks of high-fat diet,sinomenine[50 mg/(kg-d)and 100 mg/(kg-d)]was given to the low-dose group and high-dose group respectively,and the model group was given the same amount of dis-tilled water for 8 weeks.After the intervention,the serum lipid level and oxidative stress index were detec-ted,and the plaque morphology was analyzed by hematoxylin and eosin(HE)staining,Masson staining and nuclear factor erythroid 2-related factor 2(Nrf2)immunohistochemical staining,and the expression of aortic Nrf2 and downstream targeted protein was detected by Western blotting.T-test and one-way analysis of variance were used for comparison between groups.Results The body weight of mice in high dose sino-menine group was lower than that in model group[(30.910±3.741)g vs.(37.774±7.182)g,t=0.245,P＜0.05),and the level of serum total cholesterol in mice of high dose sinomenine group was de-creased[(10.30 1±2.210)mmol/L vs.(13.232±2.280)mmol/L,t=1.217,P＜0.01].The sinome-nine group showed smaller atherosclerotic plaque,less inflammatory cell infiltration,higher collagen con-tent and expression of Nrf2 and downstream target proteins in aorta.Conclusion Sinomenine can activate Nrf2 signal pathway,enhance the ability to resist oxidative stress,increase plaque stability,and has a pro-tective effect on atherosclerosis.
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