To Observe The Effect Of Evolocumab On Preventing Atherosclerotic Plaque Formation In Aop E Mice And Evaluate The Effect Of Lowing Blood Lipid

Objective: To observe the effect of evolocumab on the prevention of atherosclerotic plaque formation in Apo E mice and evaluate the effect of lowering blood lipid.Methods: With only 50 strains of Apo E-/-mice(The gene homozygosity was99%,almost no difference between individual genetically modified mice),according to random number table method is divided into A blank control group,model group B,C statin group,DPCSK9 inhibitors,E statin + PCSK9 inhibitor group,in addition to the group A,all the mice was given western purification feeding high fat forage ordinary environment.All mice were fed adaptively for one week,The blank group A and model group B were given normal saline intragastric administration,and the statins group C were given atorvastatin 10 mg /kg/d intragastric administration.The PCSK9 inhibitor group D was given 10 mg /kg subcutaneously every 2 weeks,and the statin +PCSK9 inhibitor group E was given 10 mg /kg/d atorvastatin intragastric administration and 10 mg /kg subcutaneously every 2 weeks.Executed in mice after16 weeks,serum and aorta were collected,Elisa method to detect peripheral blood of TC,TG,LDL-C,IL-1,IL-6,TNF-alpha,PCR method to detect the aortic plaques in the organization IL-1 m RNA,IL-6 m RNA,TNF-alpha m RNA expression and quantitative analysis of the plaques of nuclear factor-kappa B in the average optical density value,HE staining assay plaque area,the lumen area and the percentage of the area of the lumen area.Results: The TC,TG and LDL-C of the statin group and the PCSK9 inhibitor group and the statin +PCSK9 inhibitor group were lower than those of the model group(P < 0.01),and the TC,TG and LDL-C of the PCSK9 inhibitor group were lower than those of the statins group(P < 0.05).IL-1,IL-6 and TNF-α in the statin group,the PCSK9 inhibitor group and the statin +PCSK9 inhibitor group were lower than those in the model group(P < 0.05),and IL-1 and IL-6 in the PCSK9 inhibitor group were lower than those in the statins group(P < 0.05),and there was no statistical difference in TNF-α(P > 0.05).IL-1,IL-6 and TNF-α were decreased in the statin +PCSK9 inhibitor group compared with the statin alone group(P < 0.05).The m RNA levels of IL-1,IL-6 and TNF-α in the statin group,the PCSK9 inhibitor group and the statin +PCSK9 inhibitor group were lower than those in the model group(P < 0.05),and the m RNA levels of IL-1,IL-6 and TNF-α in the PCSK9 inhibitor group were lower than those in the statins group(P < 0.05).The quantitative expression of NF-κB in both the statin group and the PCSK9 inhibitor group was lower than that in the model group(P < 0.05),but there was no significant difference between the statin group and the PCSK9 inhibitor group(P > 0.05).Pathological observation showed that the plaque area of the model group was higher than that of the blank group(P < 0.05),and the plaque area of the statin group and the statin+PCSK9 inhibitor group was lower than that of the model group(P < 0.05).The lipid infiltration of the PCSK9 inhibitor group was less than that of the model group,and the inflammatory manifestations were reduced.Conclusion: The new lipid-lowering drug PCSK9 inhibitor has lipid-lowering and anti-inflammatory effects,and has a synergistic effect with statins.Long-term follow-up can inhibit plaques,and the mechanism may be related to the regulation of NF-κB signaling pathway.