Otani Yoshimi, Takeyoshi Izumi, Yoshinari Daisuke, Matsumoto Koshi, Morishita Yasuo
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma,Japan.
J Invest Surg. 2007 May-Jun;20(3):175-80. doi: 10.1080/08941930701365986.
Ischemia-reperfusion injury is induced by activation of the arachidonic acid cascade following the induction of cyclooxygenase-2. This study evaluated the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury in the lung. Male Wistar rats were divided into two groups. In the FK3311 group (n = 27), FK3311 (4 mg/kg) was administered intravenously 5 min before ischemia, while in the control group (n = 27) only vehicle was injected. Warm ischemia was induced for 1 h by clamping the left hilus. The arterial oxygen pressure (PaO(2)) and saturation (SaO(2)) were measured 30 and 120 min after reperfusion. Serum thromboxane B(2) and 6-keto-prostaglandin F(1alpha) were also measured 30 min after reperfusion. Lung specimens were harvested 120 min after reperfusion for histologic examination and polymorphonuclear counts, and immunostained with cyclooxygenase-2. The 1-week survival rate in the two groups was compared. PaO(2) and SaO(2) 30 and 120 min after reperfusion were significantly (p < .05) better in the FK3311 group. Serum thromboxane B(2) levels were significantly (p < .05) lower in the FK3311 group. However, there was no significant difference in 6-keto-prostaglandin F(1alpha). Histologically, tissue damage was mild and polymorphonuclear infiltration was reduced in the FK3311 group compared to the control group. The expression of cyclooxygenase-2 in the alveolar epithelium based on immunostaining was suppressed in the FK3311 group. The 1-week survival rate was significantly (p < .05) higher in the FK3311 group. We conclude that FK3311 has protective effects on pulmonary ischemia-reperfusion injury, and results in improvement in the 1-week survival rate.
缺血再灌注损伤是在环氧化酶 - 2 诱导后由花生四烯酸级联反应激活所引发的。本研究评估了选择性环氧化酶 - 2 抑制剂 FK3311 对肺脏热缺血再灌注损伤的影响。雄性 Wistar 大鼠被分为两组。在 FK3311 组（n = 27）中，在缺血前 5 分钟静脉注射 FK3311（4 毫克/千克），而在对照组（n = 27）中仅注射溶剂。通过钳夹左肺门诱导热缺血 1 小时。在再灌注后 30 分钟和 120 分钟测量动脉血氧分压（PaO₂）和血氧饱和度（SaO₂）。在再灌注后 30 分钟也测量血清血栓素 B₂和 6 - 酮 - 前列腺素 F₁α。在再灌注后 120 分钟采集肺组织标本进行组织学检查和多形核细胞计数，并用环氧化酶 - 2 进行免疫染色。比较两组的 1 周生存率。FK3311 组在再灌注后 30 分钟和 120 分钟时的 PaO₂和 SaO₂显著更好（p <.05）。FK3311 组的血清血栓素 B₂水平显著更低（p <.05）。然而，6 - 酮 - 前列腺素 F₁α没有显著差异。组织学上，与对照组相比，FK3311 组的组织损伤较轻且多形核细胞浸润减少。基于免疫染色，FK3311 组肺泡上皮中环氧化酶 - 2 的表达受到抑制。FK3311 组的 1 周生存率显著更高（p <.05）。我们得出结论，FK3311 对肺缺血再灌注损伤具有保护作用，并能提高 1 周生存率。
