贵州医科大学学报

2020, v.45;No.238(07) 760-766+772

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橙皮素对仓鼠颈动脉粥样硬化和脂质代谢的作用机制
Effect of Hesperetin on Hamster Carotid Atherosclerosis and Lipid Metabolism

覃瑛;李晓杰;许键炜;冯戎;周谊霞;
QIN Ying;LI Xiaojie;XU Jianwei;FENG Rong;ZHOU Yixia;School of Nursing,Guizhou Medical University;Department of Basic Medical Scinences,Guizhou Medical University;Health Management Medical Examination Center,Guizhou Provincial People's Hospital;

摘要(Abstract):

目的:探究橙皮素(HES)对仓鼠颈动脉粥样硬化和脂质代谢的影响。方法:将30只仓鼠均分为正常对照组(NC组)、动脉粥样硬化模型组(Model组)、HES低剂量组(L-HES组)、HES中剂量组(M-HES组)及HES高剂量组(H-HES组),后4组仓鼠均行结扎左颈总动脉的部分分支手术1周后喂饲高脂饮食,NC组仓鼠不结扎血管、且喂饲普通饲料; L-HES组、M-HES组、H-HES组仓鼠分别按50、100及150 mg/kg剂量灌胃HES、1次/d,连续干预6周,NC组及Model组给予0. 5%羧甲基纤维素钠;干预结束时,测定各组仓鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平及血清肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、单核细胞趋化蛋白1(MCP-1)含量; HE染色观察各组仓鼠颈总动脉组织学变化,实时荧光定量聚合酶链式反应(RT-qPCR)检测肝脏中低密度脂蛋白受体(LDLR)、3-羟基-3-甲基-戊二酰辅酶A还原酶(HMGCR)及胆固醇7α-羟化酶(CYP7A1) mRNA表达水平。结果:与Model组藏比较,HES可降低仓鼠血清总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白胆固醇(LDL-C)水平(P <0. 05)、但高密度脂蛋白胆固醇(HDLC)水平比较、差异无统计学意义(P> 0. 05); ELISA法检测结果示,HES能降低仓鼠血清TNF-α、IL-6和MCP-1水平(P <0. 05); HE染色结果示,Model组血管内膜中膜明显增厚,管腔明显狭窄,中膜血管平滑肌细胞以及弹性纤维排列紊乱,内膜及中膜多见针空状胆固醇结晶形成,局部可见小灶性坏死钙化,各HES剂量组颈动脉病理改变均有不同程度的改善; RT-qPCR结果示,HES可显著上调肝脏中LDLR、CYP7A1 mRNA水平,下调HMGCR mRNA水平(P <0. 05)。结论:HES可减轻动脉粥样硬化病变,其机制与下调肝脏LDLR、CYP7A1mRNA及上调HMGCR mRNA表达,降血脂和抗炎症效应有关。
Objective: To explore the effect of hesperetin( HES) on hamster carotid atherosclerosis and lipid metabolism. Methods: Thirty hamsters were randomly divided into normal control group( NC group),carotid atherosclerosis model group( Model group),low-dose HES group( L-HES group),medium-dose HES group( M-HES group) and high-dose HES group( H-HES group). Except for NC group,the hamster were partially ligated at the left carotid artery. After 1 week,NC group was continuously given standard chow diet,other groups were fed with high-fat diet. The hamsters were intragastrically administrated with HSE at a dose of 50 mg/kg( L-HES group),100 mg/kg( M-HES group) and 150 mg/kg( H-HES group) once a day for 6 weeks,and NC-and model groups were given 0. 5% CMCNa for 6 weeks. The levels of serum total cholesterol( TC),triglyceride( TG),low density lipoprotein cholesterol( LDL-C) and high density lipoprotein cholesterol( HDL-C) were measured. The levels of serum tumor necrosis factor α( TNF-α) 、interleukin-6( IL-6) and monocyte chemotactic protein 1( MCP-1) were detected by ELISA. Pathological changes of carotid artery were observed using HE staining. The real-time PCR was used to detect the mRNA expression of hepatic low density lipoprotein receptor( LDLR),3-Hydroxy-3-Methylglutaryl-CoA Reductase( HMGCR) and cholesterol 7α-hydroxylase( CYP7 A1). Results: Compared to model group,HES reduced the serum TC,TG and LDL-C levels( P < 0. 05),but not HDL-C levels( P > 0. 05). ELISA assay showed that HES decreased TNF-α,IL-6 and MCP-1 levels( P < 0. 05). HE staining showed that model group had thickened vascular intima and media,narrowed lumen,disordered arrangement of medial vascular smooth muscle cells and elastic fibers,needle-like cholesterol crystals formed in the intima and media,and locally distributed calcification of small necrotic focuses. HES treatment alleviated pathological changes of carotid artery. qPCR analysis showed that HES significantly upregulated the mRNA expression level of hepatic LDLR and CYP7 A1,and downregulated hepatic HMGCR mRNA expression level( P < 0. 05). Conclusions: HES can reduce atherosclerotic lesions by downregulating liver LDLR,CYP7 A1,upregulating HMGCR,lowering blood lipid and promoting anti-inflammation.

关键词(KeyWords): 动脉粥样硬化;脂质代谢;橙皮素;抗炎;拟人化仓鼠动物模型;仓鼠
atherosclerosis;lipid metabolism;hesperetin(HES);anti-inflammation;anthropomorphic hamster animal model;hamster

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81860089; 31360280);; 中国医学科学院中央级公益性科研院所基本科研业务费专项资金资助项目(2018PT31048)

作者(Author): 覃瑛;李晓杰;许键炜;冯戎;周谊霞;
QIN Ying;LI Xiaojie;XU Jianwei;FENG Rong;ZHOU Yixia;School of Nursing,Guizhou Medical University;Department of Basic Medical Scinences,Guizhou Medical University;Health Management Medical Examination Center,Guizhou Provincial People's Hospital;

Email:

DOI: 10.19367/j.cnki.2096-8388.2020.07.003

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