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阿米替林加重下尿路梗阻大鼠模型的纤维化过程。

Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction.

机构信息

Department of Pathology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.

出版信息

Int J Exp Pathol. 2012 Jun;93(3):218-24. doi: 10.1111/j.1365-2613.2012.00813.x. Epub 2012 May 8.

Abstract

Infravesical obstruction (IVO) secondary to benign prostatic hypertrophy can affect up to 50% of men over 50 years old and may cause serious and irreversible alterations throughout the urinary tract, especially in the bladder. Therapeutic approaches are currently limited. Amitriptyline has recently been described as an analgesic, anti-inflammatory and myorelaxant in some experimental models. The objective of this study was to investigate the effects of amitriptyline hydrochloride on the process of fibrosis in a bladder outlet obstruction model in rats. Male Wistar rats were subjected to IVO and studied at intervals of 1 and 14 days postprocedure. The rats were randomly divided into five groups: sham, IVO1-T, IVO1-NT, IVO14-T and IVO14-NT. Bladder tissue was processed for histopathology, immunohistochemistry and RT-PCR. The IVO14 groups presented bladder fibrosis, smooth muscle cell hypertrophy and bladder wall thickening. The IVO14-T group demonstrated a higher intensity of fibrosis, higher macrophage infiltration rate and higher gene expression of Transforming growth factor (TGF) Tgf-β1. Thus this data shows that in this experimental mode amitriptyline had an amplifying effect on the process of fibrosis as a whole.

摘要

下尿路梗阻(IVO)继发于良性前列腺增生,可影响多达 50%的 50 岁以上男性,可能导致整个泌尿道,尤其是膀胱发生严重且不可逆转的改变。目前治疗方法有限。阿米替林最近在一些实验模型中被描述为一种具有镇痛、抗炎和肌肉松弛作用的药物。本研究的目的是研究盐酸阿米替林对大鼠膀胱出口梗阻模型中纤维化过程的影响。雄性 Wistar 大鼠进行 IVO,并在术后 1 天和 14 天进行研究。大鼠随机分为五组:假手术组、IVO1-T 组、IVO1-NT 组、IVO14-T 组和 IVO14-NT 组。对膀胱组织进行组织病理学、免疫组织化学和 RT-PCR 检测。IVO14 组表现出膀胱纤维化、平滑肌细胞肥大和膀胱壁增厚。IVO14-T 组表现出更高强度的纤维化、更高的巨噬细胞浸润率和更高的转化生长因子(TGF)Tgf-β1 基因表达。因此,这些数据表明,在这种实验模型中,阿米替林对纤维化过程整体具有放大作用。

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