熊果酸抑制HepG2中C-反应蛋白的异常表达及其对HUVECs的损伤

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (7): 725-731.

熊果酸抑制HepG2中C-反应蛋白的异常表达及其对HUVECs的损伤

金越, 吕圆圆, 刘克辛, 韩国柱, 王长远, 刘琦, 孟强, 孙慧君

大连医科大学药学院临床药理教研室,大连 116044,辽宁

收稿日期:2012-11-07 修回日期:2013-01-07 出版日期:2013-07-26 发布日期:2013-06-20
通讯作者: 孙慧君,女,硕士生导师,教授,研究方向:心血管药理学。Tel: 0411-86110413 E-mail: sunhuijun@hotmail.com
作者简介:金越,女,博士,讲师,研究方向:心血管药理学。Tel: 0411-86110412 E-mail: rutin@sina.com
基金资助:
国家自然科学基金项目(81273508);辽宁省教育厅重点实验室项目(LS2010053);辽宁省科技厅项目(201102046);辽宁省教育厅科学研究一般项目(L2011153)

Ursolic acid inhibits over expression of CRP in HepG2 cells and CRP induced HUVECs injury

JIN Yue, LV Yuan-yuan, LIU Ke-xin, HAN Guo-zhu, WANG Chang-yuan, LIU Qi, MENG Qiang, SUN Hui-Jun

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, Liaoning, China

Received:2012-11-07 Revised:2013-01-07 Online:2013-07-26 Published:2013-06-20

摘要/Abstract

摘要： 目的: 研究不同剂量的熊果酸(UA)对IL-6诱导的HepG2细胞中C-反应蛋白(CRP)异常表达的抑制作用以及对CRP所致人脐静脉血管内皮细胞(HUVECs)损伤的保护作用。方法: IL-6(30 ng/mL)、UA(6.5、12.5、25 μmol/L)与IL-6(30 ng/mL)共同作用于HepG2细胞48 h,分别用MTT法、Western blot法及RT-PCR法检测各组细胞活力、CRP蛋白及mRNA表达情况。CRP(25 μg/mL)、UA(5,10,20 μmol/L)与CRP(25 μg/mL)共同作用于HUVECs 24 h,分别用MTT法、Western blot法及RT-PCR法检测各组细胞增殖、VCAM-1和LOX-1的蛋白及mRNA表达。结果: UA能显著抑制IL-6诱导的HUVECs细胞活力下降及细胞中CRP蛋白与mRNA的表达升高;UA显著抑制CRP引起的内皮细胞增殖,并且在mRNA及蛋白水平均能显著抑制CRP诱导的HUVECs异常高表达VCAM-1及LOX-1。结论: UA可通过抑制肝脏合成炎症因子CRP而降低血液中CRP浓度,并降低CRP等炎症因子对内皮细胞的损伤等途径从而发挥抗心肌缺血及动脉粥样硬化等心血管疾病的作用。

关键词: 熊果酸, HepG2, 人脐静脉血管内皮细胞, CRP, 动脉粥样硬化

Abstract: AIM: To investigate the inhibitory effects of ursolic acid (UA) on the over expression of C-reactive protein (CRP) induced by IL-6 in HepG2 cells and its protective effect of CRP induced human umbilical vein endothelial cells (HUVECs) injury.METHODS: HepG2 cells were treated with IL-6 (30 ng/mL) or IL-6 (30 ng/mL) and different concentrations of UA (6.5, 12.5, 25 μmol/L) for 48 h, then effect of UA on CRP-induced proliferation of HUVECs was detected by MTT assay; CRP protein and mRNA expression in HepG2 cells was detected by using Western blot and RT-PCR methods. HUVECs were treated with CRP (25 μg/mL) or CRP (25 μg/mL) and different concentrations of UA (5, 10, 20 μmol/L) for 24 h, the cell proliferation in each group was assayed by MTT and VCAM-1, LOX-1 protein or mRNA expression were detected by Western blot and RT-PCR methods.RESULTS: The cell proliferation decreasing induced by IL-6 and IL-6-induced CRP protein and mRNA expression increasing effects in HepG2 cells can be significantly inhibited by UA. Increasing cell proliferation and LOX-1/VCAM-1 abnormal over expression both on mRNA and protein levels of HUVECs induced by CRP can be markedly inhibited by different concentrations of UA.CONCLUSION: UA can reduce CRP levels in plasma by inhibiting the hepatic synthesis of CRP. So UA may have positive significance for preventing myocardial ischemia and anti-atherosclerosis diseases by preventing CRP and other inflammatory cytokines from injuring endothelial cells.

Key words: UA, HepG2, HUVECs, CRP, Atherosclerosis

中图分类号:

R965.2

金越, 吕圆圆, 刘克辛, 韩国柱, 王长远, 刘琦, 孟强, 孙慧君. 熊果酸抑制HepG2中C-反应蛋白的异常表达及其对HUVECs的损伤[J]. 中国临床药理学与治疗学, 2013, 18(7): 725-731.

JIN Yue, LV Yuan-yuan, LIU Ke-xin, HAN Guo-zhu, WANG Chang-yuan, LIU Qi, MENG Qiang, SUN Hui-Jun. Ursolic acid inhibits over expression of CRP in HepG2 cells and CRP induced HUVECs injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 725-731.

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