丙泊酚通过调控自噬改善ApoE^(-/-)小鼠动脉粥样硬化的作用及机制  

Effect and mechanism of propofol on improving atherosclerosis of ApoE^(-/-)mice by regulating autophagy

作　　者：周泓屹 姜帆[3] Zhou Hongyi;Jiang Fan(Department of Anesthesiology,Tongzhou Maternal and Child Health Hospital of Beijing,Beijing 101100,China;The First Clinical Medical School,Lanzhou University,Lanzhou 730000,China;Department of General Medicine,Beijing Luhe Hospital,Capital Medical University,Beijing 101100,China)

机构地区：[1]北京市通州区妇幼保健院麻醉科,北京101100 [2]兰州大学第一临床医学院,甘肃兰州730000 [3]首都医科大学附属北京潞河医院全科医学科,北京101100

出　　处：《兰州大学学报（医学版）》2024年第6期17-21,28,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：北京市通州区科技计划资助项目(KJ2020CX011);首都卫生发展全科医学与社区卫生科研专项资助项目(2023-2Y-014)。

摘　　要：目的 探讨丙泊酚通过调控自噬改善载脂蛋白E基因敲除(ApoE^(-/-))小鼠动脉粥样硬化(AS)的作用及机制。方法 采用C57BL6为对照组(n=5,每天腹腔注射等量生理盐水);Apo E^(-/-)小鼠随机分成模型组(n=5,每天腹腔注射等量生理盐水)、丙泊酚组[n=5,腹腔注射丙泊酚75 mg/(kg·d)^(-1)]、丙泊酚+3-甲基腺嘌呤(3-MA)组[n=5,丙泊酚75 mg/(kg·d)^(-1)+3-MA 30 mg/(kg·d)^(-1)]。对照组给予普通饲料,另3组给予高脂饲料,连续饲喂12周,造模第10周起给药,腹腔注射,1次/d。检测胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TAG)、高密度脂蛋白胆固醇(HDLC)的水平。使用苏木精-伊红染色、油红O染色以及蛋白质印迹法评估动脉的组织学结构和重组自噬效应蛋白Beclin-1(Beclin-1)、微管相关蛋白1轻链3 (LC3)-Ⅱ/LC3-Ⅰ的表达水平。结果 与对照组比较,模型组主动脉粥样斑块面积、红染脂质、血清TC、TAG、LDL-C、HDL-C均明显增加,主动脉中Beclin-1蛋白水平、LC3-Ⅱ/LC3-Ⅰ均明显升高(P<0.05);与模型组比较,丙泊酚组主动脉AS斑块面积、红染脂质、血清TC和LDL-C均显著下降(P<0.05)。主动脉中Beclin-1蛋白水平、LC3-Ⅱ/LC3-Ⅰ均明显增加(P<0.05)。与丙泊酚组比较,丙泊酚+3-MA组的主动脉AS斑块面积、红染脂质、血清TC、LDL-C均明显增加,主动脉内Beclin-1蛋白水平、LC3-Ⅱ/LC3-Ⅰ蛋白表达均显著下降(P<0.05)。结论 丙泊酚表现出对Apo E^(-/-)小鼠AS的改善作用,其机制涉及激活自噬和调节脂质代谢。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 autophagy-related proteins Beclin-1 and microtubule-associated proteins 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰwere evaluated by aortic hematoxylin-eosin staining,oil red O staining,and Western blotting techniques.Results Compared 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 propofol+3-MA group were significantly increased,and the Beclin-1 protein level and LC3-Ⅱ/LC3-Ⅰin the aorta significantly decreased(P<0.05).Conclusion Propofol show a

关 键 词：载脂蛋白E基因敲除小鼠 丙泊酚 动脉粥样硬化 自噬 

分 类 号：R614.2[医药卫生—麻醉学]