Background: Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI. Methods: Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment. Results: Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P < 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P < 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P < 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P < 0.001, and P < 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P < 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1&bgr;, interleukin-6, and tumor necrosis factor-&bgr;) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P < 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group). Conclusion: BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

中文翻译：

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Biliverdin通过抗氧化，抗炎和抗凋亡作用保护离体大鼠肺免于缺血-再灌注损伤

背景：Biliverdin（BV）对缺血再灌注损伤（IRI）具有保护作用。但是，BV对肺IRI（LIRI）的保护作用和潜在机制仍有待阐明。因此，我们旨在研究BV对LIRI的保护作用和潜在机制。方法：从Sprague-Dawley大鼠中分离出肺，以建立离体LIRI模型。在最初的15分钟稳定期后，对分离的肺进行60分钟的局部缺血，然后在进行或不进行BV治疗的情况下进行90分钟的再灌注。结果：I / R组的肺部潮气量显着下降（I / R组为1.44±0.23 ml / min，而假手术组为2.41±0.31 ml / min； P <0.001），肺顺应性（0.27±0.06） I / R组的ml / cmH2O与假手术组的0.44±0.09 ml / cmH2O; P <0.001; 1 cmH2O = 0.098 kPa），和氧气分压（PaO2）水平（I / R组为64.12±12 mmHg，而假手术组为114±8.0 mmHg； P <0.001； 1 mmHg = 0.133 kPa）。相比之下，BV组的这些参数（2.27±0.37 ml / min的潮气量，0.41±0.10 ml / cmH2O的顺应性和98.7±9.7 mmHg的PaO2）明显高于I / R组（P =分别为0.004，P <0.001和P <0.001）。与I / R组相比，超氧化物歧化酶的含量明显更高（47.07±7.91 U / mg蛋白质对33.84±10.15 U / mg蛋白质; P = 0.005），而干重比（P <0.01） ，甲烷二羧酸醛（1.92±0.25 nmol / mg蛋白质vs. 2.67±0.46 nmol / mg蛋白质; P <0.001）和三磷酸腺苷含量（297.05±47.45 nmol / mg蛋白质vs. 208.09±29.11 nmol / mg蛋白质; P = 0。005）在BV处理的肺中明显较低。组织学分析表明BV减轻了LIRI。此外，炎症细胞因子（白细胞介素-1，白细胞介素6和肿瘤坏死因子-b）的表达下调，环氧合酶2，诱导型一氧化氮合酶和Jun N端激酶的表达显着降低。 BV组（与I / R组相比，所有P <0.01）。最后，BV组的凋亡指数显着降低（与I / R组相比，P <0.01）。结论：BV通过抗氧化，抗炎和抗凋亡作用保护肺IRI。）被下调，BV组中环氧合酶2，诱导型一氧化氮合酶和Jun N末端激酶的表达显着降低（与I / R组相比，所有P <0.01）。最后，BV组的凋亡指数显着降低（与I / R组相比，P <0.01）。结论：BV通过抗氧化，抗炎和抗凋亡作用保护肺IRI。）被下调，BV组中环氧合酶2，诱导型一氧化氮合酶和Jun N末端激酶的表达显着降低（与I / R组相比，所有P <0.01）。最后，BV组的凋亡指数显着降低（与I / R组相比，P <0.01）。结论：BV通过抗氧化，抗炎和抗凋亡作用保护肺IRI。