瑞西瓜特能改善SU5416诱导的大鼠支气管肺发育不良实验模型。

IF 1.5 4区 医学 Q3 RESPIRATORY SYSTEM Experimental Lung Research Pub Date : 2021-10-01 Epub Date: 2021-09-16 DOI:10.1080/01902148.2021.1976311
Shinichi Katsuragi, Hidekazu Ishida, Hidehiro Suginobe, Hirofumi Tsuru, Renjie Wang, Chika Yoshihara, Atsuko Ueyama, Jun Narita, Ryo Ishii, Shigetoyo Kogaki, Keiichi Ozono
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引用次数: 1

摘要

背景:支气管肺发育不良(BPD)是一种常见于早产儿的慢性肺部疾病。经典的BPD是由高氧和高压机械通气引起的,而最近的BPD是由极端早产时肺血管生成和肺泡形成受损引起的。尽管有报道称西地那非对高氧诱导的大鼠BPD模型有效,但几项临床试验未能证明对BPD婴儿的呼吸状态有任何显著改善。Riociguat是一种可溶性鸟苷环化酶刺激剂,以一氧化氮独立的方式增加环鸟苷单磷酸活性。然而,对BPD的有益作用尚未确定。方法和结果:我们在第1天注射SU5416建立BPD大鼠模型,并在常氧条件下维持,导致肺泡过度简化,肺毛细血管稀疏,严重肺动脉高压,生长迟缓,这与近期临床治疗BPD的特点相似。当BPD大鼠表现出生长迟缓时,我们从第10天开始给药。组织学分析表明,瑞西奎特治疗显著但部分地改善了肺泡化、血管化和肺动脉高压。然而,氟西奎特治疗对存活率没有显著提高。结论:利奥西瓜特能改善SU5416诱导的BPD大鼠模型的肺泡化、血管化和高血压,但不能提高总生存率。
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Riociguat can ameliorate bronchopulmonary dysplasia in the SU5416 induced rat experimental model.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature neonates. Classical BPD is caused by hyperoxia and high-pressure mechanical ventilation, whereas BPD in recent era is caused by impaired pulmonary angiogenesis and alveolarization in extreme prematurity. Although sildenafil was reported to be effective in a hyperoxia-induced rat BPD model, several clinical trials could not demonstrate any significant improvement in the respiratory statuses of BPD infants. Riociguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate activity in a nitric oxide independent manner. However, a beneficial effect in BPD has not been established yet.

Methods and results: We established BPD model in rats by injection of SU5416 on day 1 followed by maintenance under normoxia, which resulted in oversimplified alveoli, sparse pulmonary capillary vessels, severe pulmonary hypertension, and growth retardation, which mimicked the features observed in recent clinical management of BPD. We administered riociguat from day 10, when BPD rats exhibited growth retardation. Histological analyses demonstrated that riociguat treatment significantly but partially ameliorated lung alveolarization, vascularization, and pulmonary hypertension. However, the survival rate was not significantly improved by riociguat treatment.

Conclusions: Riociguat could ameliorate pulmonary alveolarization, vascularization, and hypertension in the SU5416 induced BPD rat model, but could not improve the overall survival.

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来源期刊
Experimental Lung Research
Experimental Lung Research 医学-呼吸系统
CiteScore
3.80
自引率
0.00%
发文量
23
审稿时长
2 months
期刊介绍: Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia. Authors can choose to publish gold open access in this journal.
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