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吡非尼酮通过抑制膀胱纤维化改善膀胱活动低下大鼠的排尿功能。

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

机构信息

Research Support Center, School of Medicine, Keimyung University, Deagu, 42601, South Korea.

Team of Efficacy Evaluation, Orient Genia Inc, Seongnam-si, 13201, South Korea; Department of Physiology, College of Medicine, Kyung Hee University, Seoul, 02447, South Korea.

出版信息

Eur J Pharmacol. 2024 Aug 15;977:176721. doi: 10.1016/j.ejphar.2024.176721. Epub 2024 Jun 6.

Abstract

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

摘要

下尿路症状(UAB),其特征为一组症状复杂且治疗方法有限,会显著降低患者的生活质量。UAB 的特征为膀胱壁的增生和纤维化以及膀胱顺应性降低。吡非尼酮是一种强大的抗纤维化药物,可抑制特发性肺纤维化患者的纤维化进展。在目前的研究中,我们评估了吡非尼酮在 UAB 大鼠模型中治疗膀胱纤维化的疗效。UAB 通过对主要盆神经束的挤压损伤诱导。术后 42 天,用 1ml 含吡非尼酮(100、300 或 500mg/kg)的蒸馏水对吡非尼酮治疗组的大鼠进行口服,每 2 天 1 次,共 10 次,持续 20 天。神经束的挤压损伤导致排尿功能障碍,导致膀胱重量增加和膀胱中纤维相关因素的水平升高,从而导致 UAB 症状。吡非尼酮治疗可改善尿功能,增加膀胱重量并抑制纤维化因素的表达。该实验结果表明,吡非尼酮可用于改善膀胱纤维化等难以治疗的泌尿科疾病。因此,吡非尼酮治疗可被认为是改善无法治愈的 UAB 患者排尿功能的一种选择。

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