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甘露糖加重载脂蛋白E缺陷小鼠的脂蛋白代谢紊乱
王珏睿1,成晓翠1,余征真1,刘亚晋1,章卫平1,2*
0
(1. 天津医科大学朱宪彝纪念医院&天津市内分泌研究所, 国家卫生健康委员会激素与发育重点实验室, 天津 300134;
2. 海军军医大学(第二军医大学)基础医学院病理生理学教研室, 上海 200433
*通信作者)
摘要:
目的 探讨甘露糖暴露对载脂蛋白(ApoE缺陷小鼠高脂血症的影响及机制。方法 10只6周龄雄性ApoE基因缺陷小鼠采用高脂高胆固醇纯化饲料建立小鼠高脂血症模型,并分为对照组和甘露糖干预组,每组5只。对照组饲喂普通饮用水,甘露糖干预组饲喂含2%(质量体积分数)甘露糖的饮用水,持续4周。利用试剂盒检测小鼠血浆总胆固醇及甘油三酯水平,采用快速蛋白液相色谱法分离小鼠血浆脂蛋白并检测Apo和胆固醇水平,采用qPCR和蛋白质印迹法分别检测小鼠肝脏和肠道组织中脂蛋白代谢相关基因的mRNA和蛋白水平。结果 与对照组相比,甘露糖干预组小鼠的血浆甘油三酯和总胆固醇水平升高(P<0.05,P<0.01),同时伴有极低密度脂蛋白中胆固醇和ApoB100蛋白水平显著升高、高密度脂蛋白中ApoA1和ApoA4水平降低。甘露糖干预组小鼠肝脏和肠道中ApoA1蛋白表达较对照组下调,而ApoA4蛋白表达下调仅见于肠道。结论 甘露糖暴露可影响ApoE基因缺陷小鼠的脂蛋白代谢,加重高脂血症。
关键词:  甘露糖  载脂蛋白  极低密度脂蛋白  胆固醇  高脂血症
DOI:10.16781/j.CN31-2187/R.20230022
投稿时间:2023-01-28修订日期:2023-04-12
基金项目:国家自然科学基金重大研究计划(91857203),天津市教育委员会自然科学基金(2019KJ194).
Mannose aggravates lipoprotein metabolism disorder in apolipoprotein E-deficient mice
WANG Juerui1,CHENG Xiaocui1,YU Zhengzhen1,LIU Yajin1,ZHANG Weiping1,2*
(1. NHC Key Laboratory of Hormones and Development, Tianjin Institute of Endocrinology and Chu Hsien-I Memorial Hospital, Tianjin Medical University, Tianjin 300134, China;
2. Department of Pathophysiology, College of Basic Medical Sciences, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To investigate the effect and mechanism of mannose exposure on the hyperlipidemia in apolipoprotein (Apo)E-deficient mice. Methods Ten ApoE-deficient mice (6 weeks old, male) were divided into control group and mannose group (5 in each group). A hyperlipidemia model was established using high fat and high cholesterol purified feed. The mice in the control group were fed with drinking water, while the mice in the mannose group were fed with drinking water containing 2% mannose (w/v). Plasma total cholesterol and triglyceride concentrations were measured using their respective kits. Plasma lipoproteins were separated by fast protein liquid chromatography, and the Apo and cholesterol levels were measured. The mRNA and protein expression levels of lipoprotein metabolism-related genes in the liver and jejunum were detected by quantitative polymerase chain reaction and Western blotting, respectively. Results Compared with the control group, the levels of plasma triglyceride and total cholesterol of mice in the mannose group were significantly increased (P<0.05, P<0.01), accompanied by significantly higher levels of cholesterol and ApoB100 protein in very low-density lipoprotein and lower levels of ApoA1 and ApoA4 in high-density lipoprotein. The expression of ApoA1 protein in the liver and jejunum of mice in the mannose group was downregulated compared to the control group, while the downregulation of ApoA4 protein expression was only observed in the jejunum. Conclusion Mannose exposure affects lipoprotein metabolism and aggravates the hyperlipidemia in ApoE-deficient mice.
Key words:  mannose  apolipoprotein  very low-density lipoprotein  cholesterol  hyperlipidemia