基础医学与临床 ›› 2018, Vol. 38 ›› Issue (2): 163-168.

• 研究论文 • 上一篇    下一篇

小檗碱改善动脉粥样硬化小鼠的血管炎性反应和钙化

李晓明1,王青竹1,石婧1,鞠瑞1,朱蕾2,李娟3,郭磊1,叶菜英1   

  1. 1. 中国医学科学院基础医学研究所
    2. 中国医学科学院基础医学研究所&北京协和医学院基础学院
    3. 中国医学科学院基础医学研究所&北京协和医学院基础医学院
  • 收稿日期:2017-10-27 修回日期:2017-12-15 出版日期:2018-02-05 发布日期:2018-01-24
  • 通讯作者: 郭磊 E-mail:leiguo@ibms.cams.cn
  • 基金资助:
    国家自然科学基金;2016重大协同创新项目;北京协和医学院 2015 协同创新基金

Beneficial effect of berberine on atherosclerosis based on attenuating vascular inflammation and calcification

  • Received:2017-10-27 Revised:2017-12-15 Online:2018-02-05 Published:2018-01-24

摘要: 目的 以Apo-/-E小鼠和HUVEC为对象研究小檗碱对动脉粥样硬化的缓解作用。方法6~8周龄的雄性Apo-/-E小鼠随机分为对照组、模型组(给予高脂饲料喂养4周)、小檗碱组[灌胃给予,100 mg/(kg?d)]和阿托伐他汀组[灌胃给予, 5 mg/(kg?d)],每组12只。生化分析仪检测血清中TC、TG、LDL-C和HDL-C含量;ELISA检测IL-6、ALP、BMP-2和TNF-α的表达;化学发光法检测钙含量;分离主动脉并进行HE染色,免疫组化检测组织中BMP-2表达量;化学发光法检测主动脉组织匀浆中ALP的表达和钙含量。将HUVEC细胞分为对照组、模型组(TNF-α刺激)和小檗碱组(浓度分别为7.5,10,15,20 mg/L)。ELISA检测ICAM、VCAM和MMP-9表达量。结果 与对照组相比,模型组动物血清中炎性因子和血脂4项水平明显上升(P<0.05),血管内斑块明显,血管组织中ALP、BMP-2、OPG、OCN和RUNX2表达量升高(P<0.05)。小檗碱治疗后可明显降低血清中LDL-C和TC水平(P<0.05),抑制炎性因子IL-6分泌,降低血清和组织中的ALP、BMP-2、OPG、OCN、RUNX2和钙含量(P<0.05),抑制血管炎性浸润并提高斑块稳定性。与对照组相比,模型组HUVEC细胞ICAM、VCAM和MMP-9表达上调,小檗碱抑制ICAM、VCAM和MMP-9表达。结论 小檗碱能够有效调节高脂饮食动物的血清脂质水平,减少炎性介质对血管内皮的损伤并抑制血管钙化,有可能改善动脉粥样硬化发挥心血管保护作用。

关键词: 关键词:小檗碱, 动脉粥样硬化, 内皮保护, 炎性反应, 血管钙化

Abstract: Objective To investigate the beneficial effect ofberberine(BBR) on atherosclerosisin Apo-/-E mice and explore the underlying mechanisms. Methods 48 Apo-/-E mice,at 6-8 weeks old,were randomly allocated into 4 groups: Control, Model(fed with high-fat diet for 4 weeks),BBR( p.o.,100 mg/(kg?d)) and Atorvastatin (p.o., 5 mg/(kg?d))groups with 12 mice in each group.. The morphology and inflammation infiltration of aortic were examined with HE staining. The expression of BMP-2,OPG,OCN,RUNX2 in aortic was examined by immumohistochemical staining. Blood lipid levels were examined by automatic biochemical analyzer. The expression of IL-6, TNF-α and BMP-2 in serum and tissues was detected by ELISA method. The expression of ALP and the content of calcium were detected by commercially-available kits. HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24h. The contents of ICAM-1, VCAM-1, MMP-9in the culture supernatant were detected by ELISA method. Results 4-weekberberine treatment markedly reduced serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P<0.05) which was comparable with the effect of atorvastatin. Berberine also significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues (P<0.05). Berberine tended to decrease ALP, BMP-2 levels and the content of calcium in mice serum and aortic tissues (P<0.05) which were not observed in atorvastatin group. Berberine significantly reduced the levels of ICAM-1, VCAM-1, and MMP-9 in TNF-α-stimulated HUVECs. Conclusions BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet, decrease the injury caused by inflammation, and attenuate vascular calcification. It may improve atherosclerosis and play a role in cardiovascular protection.

Key words: Key words: berberine, atherosclerosis, vascular endothelium, inflammation, vascular calcification

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