Journal Article

Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects

Wen-Fang Tian Ping Weng Qiong Sheng Jun-Liang Chen Peng Zhang Ji-Ru Zhang Bin Du Min-Chen Wu Qing-Feng Pang Jian-Jun Chu

2017

Overview

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 ofreperfusion 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 FR 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 β,interleukin-6,and tumor necrosis factor-α） 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.

• Publisher: Medknow Publications and Media Pvt. Ltd,Lippincott Williams & Wilkins Ovid Technologies,Department of Pathophysiology, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, China%Department of Anesthesia, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China,Medknow Publications & Media Pvt Ltd,Wolters Kluwer
• Subject: Animals / Anti-Inflammatory Agents - therapeutic use / Antioxidants - therapeutic use / Apoptosis / Apoptosis - drug effects / Apoptosis; Biliverdin; Ischemia-reperfusion Injury; Lung; Pro-inflammatory Cytokines / Biliverdine - therapeutic use / Biotechnology / Blotting, Western / Carbon monoxide / Cyclooxygenase 2 - metabolism / Gene expression / In Situ Nick-End Labeling / Interleukin-1beta - metabolism / Interleukin-6 - metabolism / Ischemia / JNK Mitogen-Activated Protein Kinases - metabolism / Kinases / Lung - drug effects / Lung - pathology / Lungs / Lymphotoxin-alpha - metabolism / Medical schools / Nitric Oxide Synthase Type II - metabolism / Organic pigments / Original / Oxidative stress / Polymerase chain reaction / Prevention / Rats / Rats, Sprague-Dawley / Real-Time Polymerase Chain Reaction / Reperfusion injury / Reperfusion Injury - prevention & control / Rodents / Signal transduction / Superoxide Dismutase - metabolism / Transplants & implants / 保护作用 / 抗凋亡作用 / 抗氧化 / 抗炎 / 离体 / 缺血再灌注损伤 / 胆绿素 / 鼠肺