Effect and mechanism of propofol on improving atherosclerosis of Apo E-/-mice by regulating autophagy
Objective To investigate the effect and mechanism of propofol on improving atherosclerosis(AS)of apolipoprotein E gene knockout(Apo E-/-)mice by regulating autophagy.Methods C57BL6 was used as the control group(n=5,intraperitoneal injection of the same amount of normal saline every day);Apo E-/-mice were randomly divided into a model group(n=5,intraperitoneal injection of the same amount of normal saline every day),a propofol group[n=5,intraperitoneal injection of propofol 75 mg/(kg·d)-1],a propofol+3-MA(autophagy inhibitor)group[n=5,propofol 75 mg/(kg·d)-1+3-MA 30 mg/(kg·d)-1].The control group was fed with normal diet,while the other three groups received high-fat diet for 12 weeks.From the 10th week,the medication was administered via intraperitoneal injection once a day.Detection of blood lipids:cholesterol(TC),low density lipoprotein cholesterol(LDL-C),triglyceride(TAG),high density lipoprotein cholesterol(HDL-C)content.In addition,the histological structure of the arteries and the expression levels of autopha-gy-related proteins Beclin-1 and microtubule-associated proteins 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ were evalu-ated by aortic hematoxylin-eosin staining,oil red O staining,and Western blotting techniques.Results Com-pared with the control group,the aortic atherosclerotic plaque area,red-stained lipids,serum TC,TAG,LDL-C,and HDL-C in the model group were significantly increased,and the Beclin-1 protein level and LC3-Ⅱ/LC3-Ⅰ in the aorta were significantly increased(P<0.05).Compared with model group,the aortic AS plaque area,red stained lipid,TC and LDL-C in the propofol group were significantly decreased(P<0.05).At the same time,Beclin-1 protein level and LC3-Ⅱ/LC3-Ⅰ in aorta were significantly increased(P<0.05).Compared with the propofol group,the aortic AS plaque area,red dye lipid,serum TC and LDL-C in the pro-pofol+3-MA group were significantly increased,and the Beclin-1 protein level and LC3-Ⅱ/LC3-Ⅰ in the aorta significantly decreased(P<0.05).Conclusion Propofol show an improvement effect on AS in Apo E-/-mice,and its mechanism involves activation of autophagy and regulation of lipid metabolism.
apolipoprotein E gene knockout micepropofolatherosclerosisautophagy
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