罗格列酮对无糖尿病急性冠脉综合征患者外周血单核细胞合成TNF-α和组织因子的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (2): 180-185.

罗格列酮对无糖尿病急性冠脉综合征患者外周血单核细胞合成TNF-α和组织因子的影响

吴旭斌¹, 钱宗杰², 伍广伟¹, 林英忠¹, 胡昌兴¹

¹广西壮族自治区人民医院心内科, 南宁530021, 广西;
²山西医科大学第二医院心内科, 太原030001, 山西

收稿日期:2008-11-11 修回日期:2008-12-28 出版日期:2009-02-26 发布日期:2020-10-30
作者简介:吴旭斌, 男, 博士, 主治医师, 主要从事介入心脏病学基础及临床研究。Tel:15977723820 　E-mail:xubinwu@hotmail.com

Effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha and tissue factor in peripheral blood monouclear cells from patients with acute coronary syndrome without diabetes

WU Xu-bin¹, QIAN Zong-jie², WU Guang-wei¹, LIN Ying-zhong¹, HU Chang-xin¹

¹Department of Cardiology, the People's Hospital of Guangxi Zhuangzu Autonomous Region, Nanning 530021, Guangxi, China;
²Department of Cardiology, Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China

Received:2008-11-11 Revised:2008-12-28 Online:2009-02-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:研究罗格列酮对无糖尿病的急性冠脉综合征(ACS) 患者外周血单核细胞表达肿瘤坏死因子α(TNF-α) 、组织因子及组织因子活性的影响。方法:分离无糖尿病的ACS 患者外周血单核细胞。分别以不同浓度的罗格列酮(0.0 、0.1 、1.0 、10.0 μmol/L) 干预, 共同孵育24 h 后, 采用酶联免疫吸附法测定单核细胞培养上清液中TNF-α浓度及单核细胞组织因子水平, 逆转录聚合酶链式反应法检测它们的mRNA 表达, 底物发光法检测组织因子的活性。结果:罗格列酮呈剂量(0.0 、0.1 、1.0 、10.0 μmol/L) 依赖性地抑制无糖尿病的ACS 患者外周血单核细胞合成TNF-α、组织因子及组织因子活性。与0.0 、0.1 、1.0 、10.0 μmol/L浓度的罗格列酮干预相对应, 单核细胞合成TNF-α蛋白水平分别为(306 ±40) 、(262 ±32) 、(236 ±28) 、(194 ±23) ng/L, 其表达TNF-αmRNA 的相对半定量吸光值比值分别为(0.78 ±0.14) 、(0.60 ±0.09) 、(0.39 ±0.11) 、(0.30 ±0.11);单核细胞合成组织因子抗原水平分别为(5.8 ±1.3) 、(4.6 ±0.9) 、(3.3 ±0.5) 、(3.0 ±0.3) ng/L, 其表达组织因子mRNA 的相对半定量吸光值比值分别为(0.42 ±0.11) 、(0.37 ±0.10) 、(0.31 ±0.09) 、(0.22 ±0.08), 其表达组织因子活性分别为(16.2±3.2) 、(8.6 ± 2.0) 、(5.4 ± 0.6) 、(4.5 ±0.8) pmol/L(P 均<0.05)。结论:罗格列酮可抑制无糖尿病的ACS 患者外周血单核细胞合成TNF-α、组织因子及组织因子活性, 提示罗格列酮可能具有降糖外的抗炎、抗血栓作用, 从而可能在ACS 中起着潜在的重要防治作用。

关键词: 罗格列酮, 急性冠脉综合征, 肿瘤坏死因子α, 组织因子

Abstract: AIM: To study the effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha (TNF-α), tissue factor (TF), and tissue factor activity (TFA) in peripheral bloodmonouclear cells(PBMC) from patients with acute coronary syndrome (ACS) without diabetes.METHODS: The PBMC from patients with ACS without diabetes were isolated and incubated with rosiglitazone (0.0, 0.1, 1.0, 10.0 μmol/L, respectively) for 24 hours.The concentrations of TNF-αin culture medium and the levels of mononuclear cell tissue factor (MCTF) were measured by using enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions in monocytes were detected by reverse- transcriptase polymerase chain reaction (RTPCR), and TF activity was determined by chromogenic substrate assay.RESULTS: Rosiglitazone(0.0, 0.1, 1.0, 10.0 μmol/L) dose-dependently suppressed the synthesis of TNF-α, TF, and TFA in PBMC from patients with ACS without diabetes.In correspondence with the concentrations of 0.0 、0.1 、1.0 、10.0 μmol/L rosiglitazone, the levels of TNF-αprotein were respectively (306 ±40), (262 ±32), (236 ±28), (194 ± 23) ng/L, the ratios of relative semi-quantitative absorption value of TNF-αmRNA expression were respectively (0.78 ±0.14), (0.60 ±0.09), (0.39 ± 0.11), (0.30 ±0.11), the antigens levels of synthesis of TF were respectively (5.8 ±1.3), (4.6 ±0.9), (3.3 ±0.5), (3.0 ±0.3) ng/L, the ratios of relative semi-quantitative absorption value of TF mRNA expression were respectively (0.42 ± 0.11), (0.37 ± 0.10), (0.31 ±0.09), (0.22 ±0.08) and the expressions of TFA were (16.2 ±3.2), (8.6 ±2.0), (5.4 ±0.6), (4.4 ±0.8) pmol/L (all P <0.05). CONCLUSION: Our findings show that rosiglitazone reduces the synthesis of TNF-α, TF, and TFA in PBMC from patients with ACS without diabetes, that indicates rosiglitazone has the antiinflammatory and antithrombotic effects on ACS besides reducing blood glucose, and it might play a potential and important role in prevention and therapy in ACS.

Key words: rosiglitazone, acute coronary syndrome, tumour necrosis factor-alpha, tissue factor

中图分类号:

吴旭斌, 钱宗杰, 伍广伟, 林英忠, 胡昌兴. 罗格列酮对无糖尿病急性冠脉综合征患者外周血单核细胞合成TNF-α和组织因子的影响[J]. 中国临床药理学与治疗学, 2009, 14(2): 180-185.

WU Xu-bin, QIAN Zong-jie, WU Guang-wei, LIN Ying-zhong, HU Chang-xin. Effects of rosiglitazone on the synthesis of tumor necrosis factor-alpha and tissue factor in peripheral blood monouclear cells from patients with acute coronary syndrome without diabetes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 180-185.

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