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噻唑烷二酮类药物下调人血管内皮细胞中1型纤溶酶原激活物抑制剂的表达:过氧化物酶体增殖物激活受体γ在内皮功能中的可能作用。

Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function.

作者信息

Kato K, Satoh H, Endo Y, Yamada D, Midorikawa S, Sato W, Mizuno K, Fujita T, Tsukamoto K, Watanabe T

机构信息

Third Department of Internal Medicine, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.

出版信息

Biochem Biophys Res Commun. 1999 May 10;258(2):431-5. doi: 10.1006/bbrc.1999.0648.

DOI:10.1006/bbrc.1999.0648
PMID:10329404
Abstract

The effect of peroxisome proliferator-activated receptor (PPAR) gamma activators, thiazolidinediones, on plasminogen activator type 1 (PAI-1) was examined in cultured human umbilical vein endothelial cells (HUVEC). Tumor necrosis factor alpha (TNF-alpha) enhanced PAI-1 secretion and mRNA expression by approximately 2-fold. The thiazolidinediones, troglitazone and pioglitazone, decreased basal and TNF-alpha-stimulated PAI-1 secretion and mRNA expression in HUVEC in a dose-dependent fashion. PPARgamma mRNA in HUVEC could be detected by reverse transcriptase-polymerase chain reaction using specific primers. These results suggest that PPARgamma may regulate PAI-1 expression in HUVEC and that thiazolidinediones have a therapeutic potential for improving endothelial dysfunction observed in insulin resistance.

摘要

在培养的人脐静脉内皮细胞(HUVEC)中研究了过氧化物酶体增殖物激活受体(PPAR)γ激活剂噻唑烷二酮对1型纤溶酶原激活物(PAI-1)的影响。肿瘤坏死因子α(TNF-α)使PAI-1分泌和mRNA表达增加约2倍。噻唑烷二酮类药物曲格列酮和吡格列酮以剂量依赖方式降低HUVEC中基础和TNF-α刺激的PAI-1分泌及mRNA表达。使用特异性引物通过逆转录聚合酶链反应可检测到HUVEC中的PPARγ mRNA。这些结果表明PPARγ可能调节HUVEC中PAI-1的表达,且噻唑烷二酮类药物对于改善胰岛素抵抗中观察到的内皮功能障碍具有治疗潜力。

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