一氧化碳释放分子-2对小鼠广泛耐药鲍曼不动杆菌肺炎的疗效观察
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摘要
目的评价一氧化碳释放分子-2(CORM-2)对小鼠广泛耐药鲍曼不动杆菌(XDRAB)肺炎的疗效。方法通过体外抑菌试验检测CORM-2对XDRAB生长的抑制作用。再通过建立XDRAB肺炎小鼠模型,观察CORM-2对肺炎小鼠的抗菌、抗炎效果。结果 CORM-2显著下调XDRAB肺炎小鼠肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、高迁移率族蛋白B1(HMGB1)和抗炎因子IL-10的水平,抑制肺组织髓过氧化物酶(MPO)与一氧化氮(NO)的表达,减轻肺组织病理损伤,同时显著降低了肺组织内细菌负荷量。结论 CORM-2在体外和体内对XDRAB均具有显著的抑菌作用,同时在体内发挥重要的抗炎、抗氧化作用。
Objective To evaluate the efficacy of carbon monoxide-releasing molecule(CORM-2) in mouse model of pneumonia caused by extremely-drug resistant Acinetobacter baumannii(XDRAB).Methods To investigate the effect of CORM-2 on XDRAB proliferation in the bacteriostatic test in vitro.Then the mouse model of pneumonia was established by XDRAB challenge.The mice in experimental group were treated with CORM-2 by nasal insufflation.The anti-inflammatory and bacteriostatic effects of CORM-2 were analyzed by comparing with the non-treatment group.Results Compared to the control group,CORM-2 treatment significantly down-regulated the inflammatory factors of TNF-α,IL-6,HMGB1 and IL-10 in serum,inhibited the expressions of myeloperoxidase and nitrogen monoxide in lung tissues,alleviated pathological lung damage,and reduced bacterial load in lung tissues.Conclusions CORM-2 has significant bacteriostatic effect on XDRAB in vitro and in vivo.It also plays an important role in the anti-inflammatory and antioxidant process in vivo.
Objective To evaluate the efficacy of carbon monoxide-releasing molecule(CORM-2) in mouse model of pneumonia caused by extremely-drug resistant Acinetobacter baumannii(XDRAB).Methods To investigate the effect of CORM-2 on XDRAB proliferation in the bacteriostatic test in vitro.Then the mouse model of pneumonia was established by XDRAB challenge.The mice in experimental group were treated with CORM-2 by nasal insufflation.The anti-inflammatory and bacteriostatic effects of CORM-2 were analyzed by comparing with the non-treatment group.Results Compared to the control group,CORM-2 treatment significantly down-regulated the inflammatory factors of TNF-α,IL-6,HMGB1 and IL-10 in serum,inhibited the expressions of myeloperoxidase and nitrogen monoxide in lung tissues,alleviated pathological lung damage,and reduced bacterial load in lung tissues.Conclusions CORM-2 has significant bacteriostatic effect on XDRAB in vitro and in vivo.It also plays an important role in the anti-inflammatory and antioxidant process in vivo.
引文
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[15]MURRAY TS,OKEGBE C,GAO Y,et al.The carbon monoxide releasing molecule CORM-2 attenuates Pseudomonas aeruginosa biofilm formation[J].PLo S One,2012,7(4):e35499.
[16]BANG CS,KRUSE R,DEMIRE I,et al.Multiresistant uropathogenic extended-spectrumβ-lactamase(ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2(CORM-2)[J].Microb Pathog,2014,66:29-35.
[17]WILSON JL,JESSE HE,HUGHES B,et al.Ru(CO)3Cl(Glycinate)(CORM-3):a carbon monoxide-releasing molecule with broad-spectrum antimicrobial and photosensitive activities against respiration and cation transport in Escherichia coli[J].Antioxid Redox Signal,2013,19(5):497-509.
[18]DESMARD M,FORESTI R,MORIN D,et al.Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules[J].Antioxid Redox Signal,2012,16(2):153-163.
[19]NOBRE LS,AL-SHAHROUR F,DOPAZO J,et al.Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli[J].Microbiology,2009,155(3):813-824.
[20]MCLEAN S,BEGG R,JESSE HE,et al.Analysis of the bacterial response to Ru(CO)3Cl(Glycinate)(CORM-3)and the inactivated compound identifies the role played by the ruthenium compound and reveals sulfur-containing species as a major target of CORM-3 action[J].Antioxid Redox Signal,2013,19(17):1999-2012.
[2]DIJKSHOORN L,NEMEC A,SEIFERT H.An increasing threat in hospitals:multidrug-resistant Acinetobacter baumannii[J].Nat Rev Microbiol,2007,5(12):939-951.
[3]胡付品,朱德妹,汪复,等.2013年中国CHINET细菌耐药性监测[J].中国感染与化疗杂志,2014,14(5):365-374.
[4]王莉,周凤萍.ICU多重耐药鲍曼不动杆菌医院感染暴发流行病学调查[J].中国感染控制杂志,2013,12(2):113-116.
[5]ANTHONYSAMY A,BALASUBRAMANIAN S,SHANMUGAIAH V,et al.Synthesis,characterization and electrochemistry of 4'-functionalized 2,2':6',2''-terpyridine ruthenium(II)complexes and their biological activity[J].Dalton Trans,2008,16(16):2136-2143.
[6]COBURN RF.Endogenous carbon monoxide production[J].NEngl J Med,1970,282(4):207-209.
[7]CHEN P,SUN B,CHEN H,et al.Effects of carbon monoxide releasing molecule-liberated CO on severe acute pancreatitis in rats[J].Cytokine,2010,49(1):15-23.
[8]WANG X,CAO J,SUN BW,et al.Exogenous carbon monoxide attenuates inflammatory responses in the small intestine of septic mice[J].World J Gastroenterol,2012,18(40):5719-5728.
[9]MIZUGUCHI S,STEPHEN J,BIHARI R,et al.CORM-3-derived CO modulates polymorphonuclear leukocyte migration across the vascular endothelium by reducing levels of cell surface-bound elastase[J].Am J Physiol Heart Circ Physiol,2009,297(3):H920-H929.
[10]OHTSUKA T,KASEDA K,SHIGENOBU T,et al.Carbon monoxide-releasing molecule attenuates allograft airway rejection[J].Transpl Int,2014,27(7):741-747.
[11]BANI-HANI MG,GREENSTEIN D,MANN BE,et al.Acarbon monoxide-releasing molecule(CORM-3)attenuates lipopolysaccharide-and interferon-gamma-induced inflammation in microglia[J].Pharmacol Rep,2006,58Suppl:132-144.
[12]LIU DM,SUN BW,SUN ZW,et al.Suppression of inflammatory cytokine production and oxidative stress by CO-releasing molecules-liberated CO in the small intestine of thermally-injured mice[J].Acta Pharmacol Sin,2008,29(7):838-846.
[13]NOBRE LS,SEIXAS JD,ROM?O CC,et al.Antimicrobial action of carbon monoxide-releasing compounds[J].Antimicrob Agents Chemother,2007,51(12):4303-4307.
[14]DESMARD M,DAVIDGE KS,BOUVET O,et al.A carbon monoxide-releasing molecule(CORM-3)exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia[J].FASEB J,2009,23(4):1023-1031.
[15]MURRAY TS,OKEGBE C,GAO Y,et al.The carbon monoxide releasing molecule CORM-2 attenuates Pseudomonas aeruginosa biofilm formation[J].PLo S One,2012,7(4):e35499.
[16]BANG CS,KRUSE R,DEMIRE I,et al.Multiresistant uropathogenic extended-spectrumβ-lactamase(ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2(CORM-2)[J].Microb Pathog,2014,66:29-35.
[17]WILSON JL,JESSE HE,HUGHES B,et al.Ru(CO)3Cl(Glycinate)(CORM-3):a carbon monoxide-releasing molecule with broad-spectrum antimicrobial and photosensitive activities against respiration and cation transport in Escherichia coli[J].Antioxid Redox Signal,2013,19(5):497-509.
[18]DESMARD M,FORESTI R,MORIN D,et al.Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules[J].Antioxid Redox Signal,2012,16(2):153-163.
[19]NOBRE LS,AL-SHAHROUR F,DOPAZO J,et al.Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli[J].Microbiology,2009,155(3):813-824.
[20]MCLEAN S,BEGG R,JESSE HE,et al.Analysis of the bacterial response to Ru(CO)3Cl(Glycinate)(CORM-3)and the inactivated compound identifies the role played by the ruthenium compound and reveals sulfur-containing species as a major target of CORM-3 action[J].Antioxid Redox Signal,2013,19(17):1999-2012.