Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salt hypertensive rats
Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salt hypertensive rats
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DOI：
10.1097/00004872-200405000-00024
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发表时间：
2004-05-01
影响因子：
4.9
通讯作者：
Inoue, H
中科院分区：
文献类型：
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作者：
Kagitani, S;Ueno, H;Inoue, H
目的观察抗炎药N（3,4-二甲氧基肉桂酰）邻氨基苯酸（曲尼司特）是否通过抑制醋酸脱氧皮质酮（DOCA）高血压大鼠的炎症细胞浸润来抑制心肌纤维化，探讨高血压心肌纤维化与炎症细胞浸润的关系。方法sd - dawley大鼠经DOCA联合1% NaCl和0.2% KCl在左肾切除术后的饮用水中添加，给予曲尼司特（100 mg/kg / d, n = 15）或对照物（n = 15）治疗，持续4周。测定收缩压（SBP）、心肌间质纤维化、血管周围纤维化及I型、III型胶原数量，检测I型前胶原（PI）、III型前胶原（PIII）、转化生长因子(TGF)- β(1)、1型纤溶酶原激活物抑制剂（PAI-1）、单核细胞趋化蛋白（MCP）1、白细胞介素(IL)-6 mRNA表达。结果DOCA加盐治疗2周后收缩压明显升高。治疗4周后心肌间质纤维化、血管周围纤维化及胶原堆积明显增加。DOCA和盐治疗2周后，细胞中PI、PIII、tgf - β(1)、PAI-1、MCP-1、IL-6的mrna表达均显著升高。虽然曲尼司特和对照剂治疗的小鼠收缩压相似，但单核细胞/巨噬细胞浸润受到抑制，tgf - β(1)、PAI-1、MCP-1、IL-6、PI和PIII mRNA表达减弱，心肌纤维化和胶原积累受到抑制。结论DOCA/盐性高血压大鼠心肌纤维化可能与炎症/创面愈合反应有关。曲尼司特抑制单核/巨噬细胞浸润和心肌纤维化。(C) 2004利平科特·威廉姆斯·威尔金斯。
Objective In order to study the association between myocardial fibrosis and inflammatory cell infiltration in the hypertensive heart, we investigated whether N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast), an anti-inflammatory drug, would suppress myocardial fibrosis via inhibition of inflammatory cell infiltration in deoxycorticosterone-acetate (DOCA) hypertensive rats.Methods Sprague-Dawley rats treated with DOCA combined with the addition of 1% NaCl and 0.2% KCl in the drinking water after left nephrectomy were given tranilast (100 mg/kg per day, n = 15) or vehicle (n = 15) for up to 4 weeks. Systolic blood pressure (SBP), amount of myocardial interstitial fibrosis, perivascular fibrosis and type I and III collagen, and mRNA expression of procollagen I (PI) and procollagen III (PIII), transforming growth factor (TGF)-beta(1), type-1 plasminogen activator inhibitor (PAI-1), monocyte chemoattractant protein (MCP)1 and interleukin (IL)-6 were determined.Results SBP was increased significantly 2 weeks after treatment with DOCA and salt. Myocardial interstitial fibrosis, perivascular fibrosis and collagen accumulation increased significantly 4 weeks after the treatment. Two weeks after the treatment with DOCA and salt, m RNA expression of PI and PIII, TGF-beta(1), PAI-1, MCP-1 and IL-6 increased significantly. Although the SBP was similar in animals treated with tranilast or vehicle, monocyte/macrophage infiltration was suppressed, mRNA expression of TGF-beta(1), PAI-1, MCP-1, IL-6, PI and PIII was attenuated, and myocardial fibrosis and collagen accumulation were suppressed in hypertensive animals receiving tranilast.Conclusion Myocardial fibrosis seen in DOCA/salt hypertensive rats might be associated with the inflammation/wound healing response. Tranilast suppresses both infiltration of monocytes/macrophages and myocardial fibrosis. (C) 2004 Lippincott Williams Wilkins.