Shen Wei-chang, Wang Xu, Qin Wei-ting, Qiu Xue-feng, Sun Bing-wei
Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, China.
Acta Pharmacol Sin. 2014 Dec;35(12):1566-76. doi: 10.1038/aps.2014.99. Epub 2014 Nov 17.
Endogenous carbon monoxide (CO) has been shown to modulate inflammation and inhibit cytokine production both in vivo and in vitro. The aim of this study was to examine whether exogenous carbon monoxide could suppress the vitality of Escherichia coli (E coli) and improve the survival rate in an E coli-induced murine sepsis model.
ICR mice were infected with E coli, and immediately injected intravenously with carbon monoxide releasing molecule-2 (CORM-2, 8 mg/kg) or inactive CORM-2 (8 mg/kg). The survival rate was monitored 6 times daily for up to 36 h. The blood samples, liver and lung tissues were collected at 6 h after the infection. Bacteria in peritoneal lavage fluid, blood and tissues were enumerated following culture. Tissue iNOS mRNA expression was detected using RT-PCR. NF-κB expression was detected with Western blotting.
Addition of CORM-2 (200 and 400 μmol/L) into culture medium concentration-dependently suppressed the growth of E coli and decreased the colony numbers, but inactive CORM-2 had no effect. Treatment of the infected mice with CORM-2 significantly increased the survival rate to 55%, while all the infected mice treated with inactive CORM-2 died within 36 h. E coli infection caused severe pathological changes in liver and lungs, and significantly increased serum transaminases, lipopolysaccharide, TNF-α and IL-1β levels, as well as myeloperoxidase activity, TNF-α and IL-1β levels in the major organs. Meanwhile, E coli infection significantly increased the number of colonies and the expression of iNOS mRNA and NF-κB in the major organs. All these abnormalities were significantly attenuated by CORM-2 treatment, while inactive CORM-2 was ineffective.
In addition directly suppressing E coli, CORM-2 protects the liver and lungs against E coli-induced sepsis in mice, thus improving their survival.
内源性一氧化碳（CO）已被证明在体内和体外均可调节炎症并抑制细胞因子产生。本研究旨在探讨外源性一氧化碳是否能抑制大肠杆菌（E coli）的活力，并提高大肠杆菌诱导的小鼠脓毒症模型的存活率。
将ICR小鼠感染大肠杆菌，然后立即静脉注射一氧化碳释放分子-2（CORM-2，8 mg/kg）或无活性的CORM-2（8 mg/kg）。每天监测6次存活率，最长监测36小时。感染后6小时采集血样、肝组织和肺组织。培养后计数腹腔灌洗液、血液和组织中的细菌。采用RT-PCR检测组织中诱导型一氧化氮合酶（iNOS）mRNA表达。用蛋白质免疫印迹法检测核因子κB（NF-κB）表达。
在培养基中添加CORM-2（200和400 μmol/L）可浓度依赖性地抑制大肠杆菌生长并减少菌落数，但无活性的CORM-2无此作用。用CORM-2治疗感染小鼠可使存活率显著提高至55%，而所有用无活性CORM-2治疗的感染小鼠在36小时内死亡。大肠杆菌感染导致肝脏和肺脏出现严重病理变化，并显著提高血清转氨酶、脂多糖、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平，以及主要器官中的髓过氧化物酶活性、TNF-α和IL-1β水平。同时，大肠杆菌感染显著增加主要器官中的菌落数以及iNOS mRNA和NF-κB的表达。CORM-2治疗可显著减轻所有这些异常情况，而无活性的CORM-2则无效。
CORM-2除了直接抑制大肠杆菌外，还可保护小鼠肝脏和肺脏免受大肠杆菌诱导的脓毒症侵害，从而提高其存活率。
