Abstract Context: Clinical reports showed sildenafil beneficial therapy on severe chronic obstructive pulmonary disease (COPD) with pulmonary hypertension (PH) patients. Objective: The study investigated therapeutic effects of silenafil on pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats. Materials and methods: Female Sprague-Dawley rats (200–250 g) were divided into control group (no exposure, n = 10) and exposure group (n = 50) suffered from cigarette smoke exposure and Klebsiella pneumonia inhalation for 8 weeks. Then rats were orally given normal saline (control group or model group), 2.0, 3.0, or 4.5 mg/kg sildenafil for 4 weeks, respectively. Pulmonary pressure, RVHI and morphological analysis of pulmonary vascular remodeling, respiratory functions assay, morphological analysis of pulmonary alveoli, and expression of PCNA and caspase-3 of epithelial cells in bronchioles wall were examined. Results: Compared to model rats, 2.0, 3.0, and 4.5 mg/kg sildenafil increased VT by –0.6 to 9.58%, PEF by 3.12 to 6.49%, EF50 by 0.81 to 6.50%, decreased mPAP by 4.43 to 25.58%, RVHI by 6.54 to 26.41%, showing a dose-dependent improvement. Furthermore, 4.5 mg/kg sildenafil significantly increased MAN by 39.70%, LA/CSA by 37.07%, decreased muscular pulmonary arteries by 48.00%, WT by 12.83%, MT by 22.89%, caspase-3 expression by 17.71%, and showed improvement on abnormality in lung interstitial and bronchioles by microscopy. Discussion and conclusion: Our results demonstrated that sildenafil decreased pathological changes in alveoli, bronchioles, interstitial tissue, and arterioles of rats with COPD and PH.

中文翻译：

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治疗性西地那非抑制大鼠香烟烟雾暴露和细菌吸入引起的肺损伤


摘要背景：临床报告显示西地那非对严重慢性阻塞性肺疾病 (COPD) 合并肺动脉高压 (PH) 患者有益。目的：研究西那非对大鼠香烟烟雾暴露和细菌吸入引起的肺损伤的治疗作用。材料与方法：雌性Sprague-Dawley大鼠（200-250 g）分为对照组（无暴露，n = 10）和暴露组（n = 50），进行香烟烟雾暴露和肺炎克雷伯菌吸入8周。然后分别给大鼠口服生理盐水（对照组或模型组）和西地那非2.0、3.0或4.5 mg/kg，连续4周。检测肺压、RVHI及肺血管重构形态学分析、呼吸功能测定、肺泡形态学分析、细支气管壁上皮细胞PCNA、caspase-3表达。结果：与模型大鼠相比，2.0、3.0 和 4.5 mg/kg 西地那非使 VT 增加 –0.6% 至 9.58%，PEF 增加 3.12% 至 6.49%，EF50 增加 0.81% 至 6.50%，mPAP 减少 4.43% 至 25.58%，RVHI 减少6.54% 至 26.41%，显示出剂量依赖性的改善。此外，4.5 mg/kg西地那非显着使MAN增加39.70%，LA/CSA增加37.07%，肌性肺动脉减少48.00%，WT减少12.83%，MT增加22.89%，caspase-3表达减少17.71%，并显示出改善通过显微镜观察肺间质和细支气管的异常。讨论和结论：我们的结果表明，西地那非可减少 COPD 和 PH 大鼠的肺泡、细支气管、间质组织和小动脉的病理变化。