Single-dose rosuvastatin ameliorates lung ischemia-reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension

Satoshi Matsuo, Osamu Adachi, Shunsuke Kawamoto, Shinichi Fukushige, Akira Horii, Yoshikatsu Saiki, Yuriko Saiki

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Objective Lung ischemia-reperfusion (IR) injury during cardiopulmonary surgery is associated with postoperative morbidity and mortality, particularly in patients with pulmonary hypertension (PH). Using a rat model for monocrotaline-induced PH, we investigated the protective effect of rosuvastatin against IR injury in lungs affected by PH and attempted to elucidate its mechanism of action. Methods Male Sprague-Dawley monocrotaline-treated rats were divided into 4 groups (n = 8-9): sham, control + IR, statin + IR, and statin + mevalonolactone + IR. Lung ischemia was induced by left pulmonary artery occlusion (1 hour), followed by reperfusion (4 hours). Rosuvastatin (2 mg/kg) was injected 18 hours before reperfusion and mevalonolactone (1 mg/kg) was injected immediately before reperfusion. The arterial oxygen tension/inspired oxygen fraction ratio was used as a measure of lung oxygenation. Left lung tissue was analyzed for the wet-to-dry lung weight ratio and protein expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS. Macrophage recruitment was assessed by CD68 immunostaining. Results Our results showed that rosuvastatin decreased IR lung injury (control + IR vs statin + IR) in terms of the arterial oxygen tension/inspired oxygen fraction ratio (272 ± 43 vs 442 ± 13), wet-to-dry ratio (5.7 ± 0.7 vs 4.8 ± 0.6), and macrophage infiltration (8.0 ± 0.6/field vs 4.0 ± 0.5/field) (P <.05 for all). eNOS and phospho-eNOS were downregulated by IR, which was blocked by rosuvastatin. Effects of rosuvastatin were blunted by mevalonolactone. Conclusions Single-dose rosuvastatin decreased IR injury in lungs affected by PH via 2 anti-inflammatory mechanisms: preserving eNOS function and inhibiting macrophage infiltration.

本文言語English
ページ(範囲)902-909
ページ数8
ジャーナルJournal of Thoracic and Cardiovascular Surgery
149
3
DOI
出版ステータスPublished - 2015 3 1

ASJC Scopus subject areas

  • 外科
  • 呼吸器内科
  • 循環器および心血管医学

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