Study on the Effect and Mechanism of Di'ao Xinxuekang Combined with Simvastatin on Atherosclero-sis Mice
Objective To investigate the effect and mechanism of Di'ao Xinxuekang(hereinafter referred to as Xinxuekang)combined with Simvastatin on atherosclerosis(AS)mice.Methods Eight C57BL/6J mice were used as control group,and 32 ApoE-/-mice were randomly divided into model group,Xinxuekang group(160 mg·kg-1),Simvastatin group(1.3 mg·kg-1)and combined treatment group(Xinxuekang 160 mg·kg-1+Simvastatin 1.3 mg·kg-1),with eight mice in each group.The control group was fed with conventional diet,and the other four groups were fed with high-fat diet.At the same time,each administration group was given intragastric administration according to the above dose,and the volume of intragastric administration was 10 mL·kg-1,once a day for 18 weeks.After administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.Oil red O staining was used to observe the formation of aortic plaque and liver lipid accumulation in mice.Serum PCSK9 level was detected by ELISA.The mRNA and protein expression levels of LDLR,HNF1α and SREBP2 in liver tissues were detected by qRT-PCR and Western Blot.Results(1)Compared with the control group,the levels of serum TC,TG and LDL-C in the model group were significantly increased(P＜0.01),and the level of HDL-C was significantly decreased(P＜0.01).The percentage of aortic root plaque area,the percentage of total aortic plaque area and the percentage of liver lipid droplet area were significantly increased(P＜0.01).The mRNA and protein expression levels of LDLR in liver tissue were significantly decreased(P＜0.01),and the serum PCSK9 level was significantly increased(P＜0.01).The mRNA and protein expression levels of HNF1α and SREBP2 in liver tissues were significantly increased(P＜0.05,P＜0.01).(2)Compared with the model group,the levels of serum TC,TG and LDL-C in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the level of HDL-C was significantly increased(P＜0.05).The level of serum LDL-C in Simvastatin group was significantly decreased(P＜0.01).The percentage of aortic root plaque area and the percentage of total aortic plaque area in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the percentage of liver lipid droplet area in each administration group was significantly decreased(P＜0.01).The protein expression level of LDLR in liver tissue of mice in Xinxuekang group and combined treatment group was significantly increased(P＜0.05),the serum PCSK9 level was significantly decreased(P＜0.05,P＜0.01),and the mRNA and protein expression levels of HNF1 α and SREBP2 in liver tissue were significantly decreased(P＜0.05,P＜0.01).(3)Compared with the Simvastatin group,the serum HDL-C level in the combined treatment group was significantly increased(P＜0.05).The percentage of aortic root plaque area and the percentage of liver lipid droplet area were significantly decreased(P＜0.05,P＜0.01).The protein expression level of LDLR in liver tissue was significantly increased(P＜0.01),and the serum PCSK9 level was significantly decreased(P＜0.01).The expression levels of HNF1α protein and SREBP2 mRNA in liver tissues were significantly decreased(P＜0.05,P＜0.01).Conclusion Xinxuekang may play a synergistic effect on lipid-lowering and anti-AS effects of Simvastatin by inhibiting the expressions of SREBP2 and HNF1α and regulating the PCSK9/LDLR signaling pathway.
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