Tranilast prevents atrial remodeling and development of atrial fibrillation in a canine model of atrial tachycardia and left ventricular dysfunction.
曲尼司特预防房性心动过速和左心室功能障碍的犬模型的心房重构和心房颤动的发展。

摘要

OBJECTIVES:This study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model.
BACKGROUND:Tranilast inhibits transforming growth factor (TGF)-β1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear.
METHODS:Beagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses.
RESULTS:Atrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-β1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-β1, 1.28 ± 0.20, p < 0.05 vs. control).
CONCLUSIONS:Tranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-β1 and Rac1 overexpression may contribute to its antiremodeling effects.

译文

目的: 本研究旨在评估曲尼司特对犬心房颤动 (AF) 模型心房重构的影响。
背景: 曲尼司特抑制转化生长因子-β 1,并在许多病理生理环境中预防纤维化。然而,曲尼司特对心房重构的影响尚不清楚。
方法: 比格犬在接受安慰剂 (对照组犬,n = 8) 或曲尼司特 (曲尼司特犬,n = 10) 治疗的同时,进行 4 周的心房快速收缩 (400 次/分钟)。Sham dogs (n = 6) 没有接受心房快速收缩。房室传导得以保留。由于快速心室反应,控制犬和曲尼司特犬出现心室功能障碍。
结果: 在对照组中,心房颤动持续时间 (211 ± 57 s) 增加,AF 周期长度和心房有效不应期缩短,但是这些变化在曲尼司特犬中被抑制 (AF 持续时间, 18 ± 10 s,p <0.01 vs. 控制)。L 型钙通道 α 1c (Cav1.2) 微核糖核酸表达在对照犬中下降 (假 1.38 ± 0.24 vs. 对照 0.65 ± 0.12,p <0.01),但在曲尼司特犬中没有 (0.97 ± 0.14,p = 与假手术组相比不显著)。显著的心房纤维化 (纤维组织面积,假 0.8 ± 0.1 vs. 对照 9.3 ± 1.3%,p <0.01) 和金属蛋白酶组织抑制剂蛋白 1 的表达在对照犬中观察到增加,但在曲尼司特犬中没有观察到 (纤维组织面积,1.4 ± 0.2%, p <0.01 vs. 控制)。Tgf-β 1 (假 1.00 ± 0.07 vs. 对照 3.06 ± 0.87,p <0.05) 和 Rac1 蛋白在对照犬中过表达,但在曲尼司特犬中过表达受到抑制 (tgf-β 1,1.28 ± 0.20,p <0.05 vs. 控制)。
结论: 曲尼司特可预防犬模型的心房重构并抑制 AF 的发展。其抑制 tgf β 1 和 Rac1 过表达可能有助于其抗重塑作用。

Tranilast

呼吸 过敏反应介质阻释药 药物
概述  :  

曲尼司特70年代由日本学者Koda等研制成功,可抑制过敏介质的释放,于1982年上市。有学者发现其可抑制同源被动皮肤过敏反应,主要抑制肥大细胞产生IgE抗体及其释放的炎症介质组胺而发挥作用。随后,有学者发现曲尼司特对儿童支气管哮喘具有良好的控制作用。1987年发现它能抑制成纤维细胞在体外的增殖,并选择性地抑制胶原蛋白在体内的沉积,从而用于治疗肥厚性瘢痕和瘢痕疙瘩。随着其药理作用的不断阐明,其临床应用也日益广泛。 临床应用 曲尼司特在临床上

Tranilast   /trænɪ'læst/

释    义   曲尼司特

例    句   Compound tranilast capsules is a safe and effective antiasthma drug. 复方曲尼司特胶囊是一种安全有效的平喘药。

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