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| Effects of hydrogen sulfide on mitochondria of lung tissue in acute lung injury induced by sepsis in rats |
| Du Quan-sheng, He Cong, Ren Shan, Yu Di, Wang Jing-mei |
| Intensive Care Unit, Hebei General Hospital, Shijiazhuang 050051, China |
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Abstract Objective To observe the effects of H2S on structure and function of mitochondria of lung tissue in acute lung injury (ALI) induced sepsis in rats. Methods Eighty male rats were randomly divided into five groups. Sham operation group, ALI group, low dose NaHS group, middle dose NaHS group, high dose NaHS group. Rats were anaesthetized. Cecal ligation and puncture (CLP) technique was used to make the rat models of sepsis．In low, middle and high dose NaHS groups, NaHS (0.78, 1.56 and 3.12 mg/kg) was respectively administrated at 30 min before CLP. Saline (2mL/kg) was administrated in Sham operation group and ALI group. The rats were respectively sacrificed 12 h after CLP. We measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. The lung tissue was quickly excised and was homogenated. The mitochondria are isolated with differential centrifugation. Ultrastructure of lung mitochondria was observed using an electron microscope. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in lung mitochondria and the mitochondrial swelling and activity were determined. Results Compared to the Sham operation group, wet-to-dry weight ratio and interleukin-1 β content in the ALI group were significantly increased. Compared with those of ALI group, wet-to-dry weight ratio and interleukin-1 β content in low, middle and high dose NaHS groups were significantly decreased. Transmission electron microscope showed that there were significant differences between the mitochondrial ultrastructure in the Sham operation group and ALI group in rat lung cells. The mitochondria in rat lung cells was swollen with disrupted or disintegrated cristae, and the osmiophilic lamellar bodies had fused or disappeared in ALI injury group. Compared with those of ALI group, the mitochondrial damage was slightly mitigated in the low-dose NaHS group and significantly mitigated in the middle-dose and high-dose NaHS groups in rats. Compared with those of Sham operation, the MDA content was significantly increased and the SOD, GSH-PX activities significantly decreased in lung mitochondria in the ALI group in rats. Compared with those of the ALI group, the MDA content was significantly decreased and the SOD, GSH-PX activities were significantly increased in lung mitochondria in low, middle and high dose NaHS groups in rats. Compared with those of Sham operation group, the swelling of the lung mitochondria was significantly increased and the activity of the lung mitochondria was significantly decreased in the ALI group in rats. In the low, middle and high dose NaHS groups, the swelling of the lung mitochondria was markedly decreased and the activity of the lung mitochondria was markedly increased compared with those of the ALI group in rats. Conclusion H2S has a beneficial effect against ALI induced by sepsis with decreasing the mitochondrial lipid peroxidation level and protecting the lung tissue cell structure and function.
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Corresponding Authors:
Wang Jing-mei, E-mail： wjmrgs12345@yeah.net
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| ［1］Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome［J］. J Clin Invest, 2012, 122（8）:2731-2740.
［2］Dushianthan A, Grocott MP, Postle AD, et al.Acute respiratory distress syndrome and acute lung injury［J］. Postgrad Med J, 2011, 87（1031）:612-622.
［3］Ruchko MV, Gorodnya OM, Zuleta A, et al. The DNA glycosylase Ogg1 defends against oxidant-induced mtDNA damage and apoptosis in pulmonary artery endothelial cells［J］.Free Radic Biol Med, 2011, 50（9）:1107-1113.
［4］Wallace JL, Wang R. Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter［J］. Nat Rev Drug Discov, 2015, 14（5）: 329-345.
［5］Wang R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed［J］. Physiol Rev, 2012, 92（2）:791-896.
［6］Wagner F, Asfar P, Calzia E, et al. Bench-to-bedside review:Hydrogen sulfide-the third gaseous transmitter:applications for critical care［J］. Crit Care, 2009, 13（3）: 213.
［7］Wang C, Wang HY, Liu ZW, et al. Effect of endogenous hydrogen sulfide on oxidative stress in oleic acid-induced acute lung injury in rats［J］. Chin Med J (Engl), 2011, 124（21）: 3476-3480.
［8］黄继义, 叶先龙, 刘才文, 等. 硫化氢对脂多糖诱导急性肺损伤的保护作用［J］. 中国急救医学, 2012, 32（10）:907-909.
［9］Faller S, Spassov SG, Zimmermann KK, et al. Hydrogen sulfide prevents hyperoxia-induced lung injury by downregulating reactive oxygen species formation and angiopoietin-2 release［J］. Curr Pharm Des, 2013, 19（15）: 2715-2721.
［10］Rittirsch D, Huber-Lang MS, Flierl MA, et a1. Immunodesign of experimental sepsis by cecal ligation and puncture［J］. Nat Protoc， 2009，4（1）：31-36.
［11］刘蓓蓓，陈娣，潘昊，等. 硫化氢在脓毒症大鼠肺损伤中的作用［J］. 中国急救医学， 2013， 33（5）:394-398.
［12］杜全胜，张萌，李国风，等. 硫化氢对脂多糖致ALI大鼠肺组织线粒体的影响［J］. 中华危重病急救医学，2017，29（1）:30-33.
［13］Reiss OK. Studies of lung metabolism. I. Isolation and properties of subcellular fractions from rabbit lung［J］. J Cell Biol, 1966, 30 （1）: 45-57.
［14］Chattipakorn SC, Thummasorn S, Sanit J, et al. Phosphodiestera〖JP〗se-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart［J］. J Geriatr Cardiol, 2014, 11（2）: 151-157.
［15］Dogan SA, Trifunovic A. Modelling mitochondrial dysfunction in mice［J］. Physiol Res, 2011, 60:S61-S70.
［16］Trentadue R, Fiore F, Massaro F, et al. Induction of mitochondrial dysfunction and oxidative stress in human fibroblast cultures exposed to serum from septic patients［J］. Life Sci, 2012, 91（7-8）:237-243.
［17］Chouteau JM, Obiako B, Gorodnya OM, et al. Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs［J］. Am J Physiol Lung Cell Mol Physiol, 2011, 301（6）:L892-L898. |
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