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布美他尼对慢性阻塞性肺疾病模型大鼠肺损伤的影响及机制
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| 篇名： | 布美他尼对慢性阻塞性肺疾病模型大鼠肺损伤的影响及机制 |
| TITLE： | Effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease model rats |
| 摘要： | 目的 探讨布美他尼对慢性阻塞性肺疾病（COPD）大鼠肺损伤的影响及机制。方法采用脂多糖诱导构建COPD大鼠模型。将造模成功的大鼠随机分为模型组（COPD组），布美他尼低、高剂量组（Bumetanide-L组、Bumetanide-H组），布美他尼高剂量+Yes相关蛋白/含有PDZ结合基序的转录共激活因子（YAP/TAZ）信号通路激活剂组（Bumetanide-H+PY-60组），每组12只；另取12只正常大鼠作为正常对照组（Control组）。大鼠造模前30min，单次吸入布美他尼/生理盐水或（和）尾静脉单次注射PY-60/生理盐水。造模给药结束次日，检测各组大鼠肺功能指标[0.3s用力呼气容积（FEV0.3）、用力肺活量（FVC）、呼气流量峰值（PEF）、FEV0.3/FVC]，测定其支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β水平，观察其肺组织病理形态和肺纤维化程度，检测其肺组织中转化生长因子β（TGF-β）、α-平滑肌肌动蛋白（α-SMA）、TAZ蛋白表达水平和YAP蛋白磷酸化水平。结果与COPD组比较，Bumetanide-L组、Bumetanide-H组大鼠肺组织病理损伤均减轻，肺上皮细胞脱落及管壁增厚情况和肺纤维化程度均减轻，炎症细胞浸润和蓝色胶原沉积均减少；FEV0.3、FVC、FEV0.3/FVC、PEF均显著升高（P＜0.05）；肺损伤评分，TNF-α、IL-6、IL-1β水平及TGF-β、α-SMA、TAZ蛋白表达水平和YAP蛋白磷酸化水平均显著降低（P＜0.05）。PY-60能显著逆转布美他尼对上述指标的改善作用（P＜0.05）。结论布美他尼可减轻COPD大鼠肺损伤，改善炎症反应及肺纤维化，其作用机制与抑制YAP/TAZ信号通路相关。 |
| ABSTRACT： | OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway. |
| 期刊： | 2025年第36卷第08期 |
| 作者： | 雷宇；陆婧；贺文娟；顾佳颖；周登峰 |
| AUTHORS： | LEI Yu，LU Jing，HE Wenjuan，GU Jiaying，ZHOU Dengfeng |
| 关键字： | 布美他尼；慢性阻塞性肺疾病；YAP/TAZ信号通路；肺损伤；肺纤维化 |
| KEYWORDS： | bumetanide； chronic obstructive pulmonary |
| 阅读数： | 2 次 |
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