研究论文 RESEARCH PAPER

苜蓿素对高脂饲粮诱发的大鼠血管内皮损伤的治疗作用

  • 郭炎峰 ,
  • 郭海海 ,
  • 范玉雪 ,
  • 程国强 ,
  • 玉永雄
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  • 1. 西南大学动物科学技术学院, 重庆 404100;
    2. 重庆市渝北区王家街道社区事务服务中心, 重庆 401120
郭炎峰(1995-),男,河南洛阳人,硕士研究生,动物营养与饲料科学专业。E-mail:1159645023@qq.com

收稿日期: 2022-03-10

  网络出版日期: 2022-10-17

基金资助

西南山地生态循环农业国家级培育基地项目;国家重点基础研究发展规划项目(2014CB138701)

Therapeutic Effects of Ticin on High-Fat Diet-Induced Vascular Endothelial Injury in Rats

  • GUO Yanfeng ,
  • GUO Haihai ,
  • FAN Yuxue ,
  • CHENG Guoqiang ,
  • YU Yongxiong
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  • 1. School of Animal Science and Technology, Southwest University, Chongqing 404100, China;
    2. Community Affairs Service Center, Wangjia Street, Yubei District, Chongqing 401120, China

Received date: 2022-03-10

  Online published: 2022-10-17

摘要

本试验旨在研究苜蓿素对高脂饲粮诱发的大鼠血管内皮损伤的治疗作用。将50只SD大鼠随机分为5组,即空白对照组、高脂模型组、辛伐他汀治疗组[1.8 mg/(kg·d)]和低剂量苜蓿素治疗组[5 mg/(kg·d)]及高剂量苜蓿素治疗组[15 mg/(kg·d)],每组10个重复,每个重复1只。除空白对照组外,其余各组均采用高脂饲粮喂养构建大鼠血管内皮损伤模型,建模周期和治疗周期各为5周,建模结束(第36天)时,测定空白对照组和高脂模型组大鼠的血脂相关指标,并通过苏木精-伊红(HE)染色观察主动脉形态学变化。治疗结束(第70天)时,检测各组大鼠的血脂相关指标及观察主动脉形态学变化,微量法检测血清中乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,酶联免疫分析法测定大鼠血清中炎症相关因子含量,Western blot法测定大鼠主动脉核因子-κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路蛋白表达。结果表明:1)建模结束时,与空白对照组相比,高脂模型组大鼠血脂异常,血管内皮可见连续多处损伤,血管内皮和皮下组织均明显增厚,且内皮局部向管腔明显隆起,表明建模成功。2)治疗结束时,与模型组相比,各治疗组大鼠血脂水平均出现明显改善,主动脉内皮无损伤状况,血清SOD活性极显著升高(P < 0.01),血清LDH活性(除低剂量苜蓿素治疗组)和MDA含量显著降低(P < 0.05),炎症相关因子[肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)]的含量或活性及NF-κB和MAPK信号通路蛋白[NF-κB p65蛋白(p65)、NF-κB抑制蛋白α(IKB)、磷酸化NF-κB p65蛋白(P-p65)、磷酸化NF-κB抑制蛋白α(P-IKB)、p38丝裂原活化蛋白激酶(p38MAPK)、c-Jun氨基末端激酶(JNK)、细胞外调节蛋白激酶1/2(ERK1/2)、磷酸化p38丝裂原活化蛋白激酶(P-p38)、磷酸化c-Jun氨基末端激酶(P-JNK)、磷酸化细胞外调节蛋白激酶1/2(P-ERK1/2)]表达量和磷酸化水平均极显著降低(P < 0.01),而且高剂量苜蓿素治疗组对炎症通路蛋白表达的抑制效果强于辛伐他汀治疗组。综上所述,苜蓿素能够通过降血脂、抗氧化、消炎等多种途径修复高脂饲粮诱发的大鼠血管内皮损伤。

本文引用格式

郭炎峰 , 郭海海 , 范玉雪 , 程国强 , 玉永雄 . 苜蓿素对高脂饲粮诱发的大鼠血管内皮损伤的治疗作用[J]. 动物营养学报, 2022 , 34(10) : 6768 -6780 . DOI: 10.3969/j.issn.1006-267x.2022.10.069

Abstract

To study the therapeutic effects of tricin on high-fat diet-induced vascular endothelial injury in rats, fifty SD rats were randomly divided into 5 groups, including blank control group, high-fat model group, simvastatin treatment group [1.8 mg/(kg·d)], low-dose tricin treatment group [5 mg/(kg·d)] and high-dose tricin treatment group [15 mg/(kg·d)]. There were 10 replicates in each group, and each replicate had 1 SD rat. Except the blank control group, all rats in the other groups were fed a high-fat diet to establish rat vascular endothelial injury models. Both modeling period and treatment period took 5 weeks. At the end of modeling (day 36), the blood lipid related indexes of the rats in the blank control group and the high-fat model group were measured, and the morphological changes of the aorta were observed by HE staining. At the end of the treatment (day 70), the serum related lipid indexes of the rats in each group were detected and the morphological changes of the aorta were observed. The lactate dehydrogenase (LDH), superoxide dismutase (SOD) activities and malondialdehyde (MDA) content in serum were detected by micro-assay. The contents of inflammation-related factors in serum were detected by enzyme-linked immunoassay (ELISA). Western blot was used to determine the protein expression of nuclear factor -κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway in aorta. Results showed as follows: 1) after modeling, compared with the blank control group, the rats in the high-fat model group had dyslipidemia and damaged aortic endothelium. Vascular endothelium and subcutaneous tissue were significantly thickened, and the local endothelium bulges significantly towards the lumen, indicating that the modeling was successful. 2) After treatment, compared with the model group, the serum lipid levels of the rats in each treatment group were significantly improved, and the aortic endothelium was not damaged. The activity of SOD in serum significantly increased (P < 0.01), and LDH activity (except for low-dose tricin treatment group) and MDA content in serum decreased (P < 0.05), and the content or activity of inflammation-related factors [tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2), interleukin-1 (IL-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)], and the expression levels and phosphorylation levels of NF-κB and MAPK signaling pathway proteins [(NF-κB p65 protein (p65), NF-κB inhibitory protein α (IKB), phosphorylated NF-κB p65 protein (P-p65), phosphorylated NF-κB inhibitory protein α (P-IKB), p38 mitogen kinase (p38MAPK), c-Jun amino-terminal kinase (JNK), extracellular regulatory protein kinase 1/2 (ERK1/2), phosphorylated p38 mitogen kinase (P-p38), phosphorylated Jun-amino-terminal kinase (P-JNK), phosphorylated extracellular regulatory protein kinase 1/2 (P-ERK1/2)] significantly decreased (P < 0.01), and high-dose tricin treatment group had a stronger inhibitory effect on the expression of inflammatory pathway proteins than simvastatin treatment group. The results show that tricin can repair vascular endothelial damage through various ways such as lowering blood lipids, anti-oxidation and anti-inflammatory.

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