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地蒽酚对博来霉素诱导的大鼠肺纤维化的保护作用。

Protective effect of dapsone against bleomycin-induced lung fibrosis in rat.

机构信息

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Exp Mol Pathol. 2022 Feb;124:104737. doi: 10.1016/j.yexmp.2021.104737. Epub 2021 Dec 22.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial disease of the lung tissue that causes symptoms such as coughing and asthma. It is caused by inflammatory factors and oxidative stress. In vivo model of IPF is induced by bleomycin (BLM,) a chemotherapeutic agent. We have investigated the effect of dapsone on bleomycin-induced IPF in adult male Wistar rats due to its anti-inflammatory and anti-oxidative stress effects. The animals were randomly divided into 5 groups (Control, BLM, BLM + dapsone 1, BLM + Dapsone 3, BLM + Dapsone 10). The control group received normal water and food. In the fibrosis group, bleomycin (BLM) (5 mg/kg) was used to induce pulmonary fibrosis by intratracheal administration. Three groups of animals were treated daily with single doses of 1, 3, and 10 mg dapsone by intraperitoneal injection 1 h after receiving BLM for 2 weeks. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and oxidative stress markers such as myeloperoxidase (MPO), malondialdehyde (MDA), protein carbonyl (PC) and nitrite were measured to evaluate bleomycin and therapeutic effect of dapsone. The histological assays of lung tissues were done by Hematoxylin-eosin (H & E) and Masson's trichrome staining. BLM reduced the activity of oxidative enzymes and increased the oxidative stress markers, while treatment with dapsone has reversed the results. In addition, the total number of cells as inflammatory cells such as neutrophils and eosinophils were examined. It has been indicated BLM increased these cells, and dapsone decreased them. The results of H & E and Masson's trichrome staining showed that dapsone reduced inflammation and alveolar wall thickness and BLM-induced pulmonary fibrosis. According to the findings of this study, dapsone seems to have therapeutic effects on pulmonary fibrosis through its anti-inflammatory and anti-oxidative stress properties and reduction of the toxic effects of bleomycin.

摘要

特发性肺纤维化(IPF)是一种慢性肺组织间质性疾病,可引起咳嗽和哮喘等症状。它是由炎症因子和氧化应激引起的。体内 IPF 模型是通过博来霉素(BLM)诱导的,BLM 是一种化疗药物。我们研究了氨苯砜对博来霉素诱导的成年雄性 Wistar 大鼠 IPF 的影响,因为它具有抗炎和抗氧化应激作用。动物随机分为 5 组(对照组、BLM 组、BLM+氨苯砜 1 组、BLM+氨苯砜 3 组、BLM+氨苯砜 10 组)。对照组给予正常水和食物。在纤维化组中,通过气管内给药给予博来霉素(BLM)(5mg/kg)诱导肺纤维化。三组动物在接受 BLM 后 1 小时内每天腹腔注射单次剂量 1、3 和 10mg 氨苯砜,共 2 周。测量抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性以及髓过氧化物酶(MPO)、丙二醛(MDA)、蛋白羰基(PC)和亚硝酸盐等氧化应激标志物,以评估 BLM 和氨苯砜的治疗效果。通过苏木精-伊红(H&E)和 Masson 三色染色对肺组织进行组织学检测。BLM 降低了氧化酶的活性并增加了氧化应激标志物,而氨苯砜治疗则逆转了这些结果。此外,还检查了作为中性粒细胞和嗜酸性粒细胞等炎症细胞的总细胞数。结果表明 BLM 增加了这些细胞,而氨苯砜减少了这些细胞。H&E 和 Masson 三色染色的结果表明,氨苯砜通过其抗炎和抗氧化应激特性以及减少博来霉素的毒性作用来减轻炎症和肺泡壁厚度以及 BLM 诱导的肺纤维化。根据这项研究的结果,氨苯砜似乎通过其抗炎和抗氧化应激特性以及减少博来霉素的毒性作用对肺纤维化具有治疗作用。

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