Tranilast attenuates vascular hypertrophy, matrix accumulation and growth factor overexpression in experimental diabetes
Tranilast attenuates vascular hypertrophy, matrix accumulation and growth factor overexpression in experimental diabetes
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DOI：
10.1016/s1262-3636(07)70049-6
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发表时间：
2003-09-01
影响因子：
7.2
通讯作者：
Gilbert, RE
中科院分区：
文献类型：
--
作者：
Bonnet, F;Cao, Z;Gilbert, RE
目的：生长因子转化生长因子- β (tgf - β)和表皮生长因子（EGF）都与血管肥厚结构变化有关，这是人类和实验性糖尿病的特征。最近，曲那司特（N（3,4-二甲氧基肉桂酰）邻氨基苯酸），一种用于治疗过敏性和皮肤病的药物，也被报道可以抑制转化生长因子- β (tgf - β)介导的胶原形成。然而，其对糖尿病血管肥大的影响尚不清楚。因此，本研究旨在确定曲尼司特对tgf - β和EGF表达以及肥大细胞介导实验性糖尿病营养血管变化的影响。方法：用曲尼司特（200 mg/kg/d）和不加曲尼司特（200 mg/kg/d）治疗3周，观察各组大鼠肠系膜动脉血管形态、生长因子、胶原基因表达和基质沉积。结果：与对照动物相比，糖尿病大鼠血管重量、壁腔比、ECM积累、tgf - β 1、EGF以及α 1(1)和α 1 （IV）胶原蛋白基因表达均显著增加。曲尼司特治疗不影响血糖或全身血压。然而，曲尼司特显著降低了糖尿病大鼠肠系膜重量、壁腔比和基质沉积，并减弱了tgf - β 1、EGF以及α 1(1)和α 1 （IV）胶原mRNA的过表达。结论：这些研究结果表明曲尼司特改善了实验性糖尿病中观察到的与生长因子表达降低相关的病理性血管变化，而不依赖于血糖或全身血压。
Objectives: The growth factors transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) have both been implicated in the hypertrophic structural changes in the vasculature that are characteristic features of both human and experimental diabetes. Recently, tranilast (N (3,4-dimethoxycinnamoyl)anthranilic acid), a drug used in the treatment of allergic and dermatological diseases, has also been reported to inhibit transforming growth factor-beta (TGF-beta)-mediated collagen formation. However, its effects on vascular hypertrophy in diabetes are unknown. The present study thus sought to determine the effects of tranilast on both TGF-beta and EGF expression and mast cells in mediating the trophic vascular changes in experimental diabetes.Methods: Vessel morphology, growth factors and collagen gene expression and matrix deposition were examined in the mesenteric arteries of control rats treated with or without tranilast, and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without tranilast (200 mg/kg/day) during a 3-week period.Results: Compared with control animals, diabetic rats had significantly increased vessel weight, wall: lumen ratio, ECM accumulation, gene expression of TGF-beta1, EGF, and both alpha1 (1) and alpha1 (IV) collagen. Tranilast treatment did not influence plasma glucose or systemic blood pressure. However, tranilast significantly reduced mesenteric weight, wall: lumen ratio and matrix deposition and also attenuated the overexpression of TGF-beta1, EGF, and both alpha1 (1) and alpha1 (IV) collagen mRNA in diabetic rats.Conclusion: These findings indicate that tranilast ameliorates pathological vascular changes observed in experimental diabetes in association with reduced growth factor expression independent of blood glucose or systemic blood pressure.