博来霉素诱导性肺动脉高压和肺纤维化的内皮素受体拮抗剂波生坦改善作用。
Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan.
机构信息
Department of Internal Medicine II, Pneumology, University of Regensburg, Regensburg, Germany.
出版信息
Respir Physiol Neurobiol. 2010 Jan 31;170(1):32-6. doi: 10.1016/j.resp.2009.11.005. Epub 2009 Nov 28.
RATIONALE
There is evidence that endothelin plays a key role in the development of pulmonary hypertension (PH) in pulmonary fibrosis (PF). However, the functional consequence of the unselective endothelin receptor antagonist Bosentan in PH and PF has not yet been studied. Therefore, we investigated the effects of Bosentan on the development of PH in the model of Bleomycin-induced PF in rats.
METHODS
Adult male Wistar rats were randomly assigned to the following groups: untreated animals (controls), Bleomycin-induced PF (Bleomycin) and Bleomycin-induced PF treated with Bosentan (Bleomycin+Bosentan). Exercise capacity was evaluated by treadmill exercise testing. PH was assessed by right ventricular systolic pressure (RVSP) and right ventricular hypertrophy. For quantification of PF the hydroxyproline content in lung tissue (HPC) was measured.
RESULTS
Compared to controls, animals with Bleomycin-induced PF showed a significant reduction in exercise capacity (44% vs. 100%), significantly higher RVSP (65 mmHg vs. 23 mmHg), significantly more right ventricular hypertrophy (0.55 vs. 0.24) and significantly higher HPC (60.5 vs. 14.8). Bosentan treatment in animals with Bleomycin-induced PF resulted in significantly greater exercise capacity (98% vs. 44%) and a trend towards lower RVSP (52 mmHg vs. 65 mmHg), significantly less right ventricular hypertrophy (0.34 vs. 0.55) and significantly lower HPC (16.7 vs. 60.5) compared to untreated Bleomycin-induced PF.
CONCLUSION
Application of Bosentan in Bleomycin rats resulted in significantly higher exercise capacity as a result of improvements in PH and PF.
背景
有证据表明，内皮素在肺纤维化（PF）所致肺动脉高压（PH）的发展中起关键作用。然而，非选择性内皮素受体拮抗剂波生坦在 PH 和 PF 中的功能后果尚未得到研究。因此，我们研究了波生坦对博来霉素诱导的 PF 大鼠模型中 PH 发展的影响。
方法
成年雄性 Wistar 大鼠被随机分为以下几组：未治疗的动物（对照组）、博来霉素诱导的 PF（博来霉素）和博来霉素诱导的 PF 用波生坦治疗（博来霉素+波生坦）。通过跑步机运动测试评估运动能力。通过右心室收缩压（RVSP）和右心室肥厚评估 PH。为了定量评估 PF，测量肺组织羟脯氨酸含量（HPC）。
结果
与对照组相比，博来霉素诱导的 PF 动物的运动能力显著降低（44%比 100%），RVSP 显著升高（65mmHg 比 23mmHg），右心室肥厚显著增加（0.55 比 0.24），HPC 显著增加（60.5 比 14.8）。博来霉素诱导的 PF 动物用波生坦治疗后，运动能力显著提高（98%比 44%），RVSP 有降低趋势（52mmHg 比 65mmHg），右心室肥厚显著减少（0.34 比 0.55），HPC 显著降低（16.7 比 60.5）。
结论
波生坦在博来霉素大鼠中的应用显著提高了运动能力，这是由于 PH 和 PF 的改善。
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