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| Inhibitory effect of suramin on inflammatory response in pulmonary tissue and peripheral blood in LPS-induced septic mice |
| HAN Liang1,2, HOU Jin-chao1, FANG Xiang-ming1 |
1. Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
2. Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China |
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Abstract Objective:To investigate the effect of suramin on inflammatory response in pulmonary tissue and peripheral blood in septic mice.Methods:Twenty-four male C57BL/6 mice were randomly divided into two groups, and suramin(5 mg/kg) or normal saline was intravenously injected 30 min before LPS(5 mg/kg)infusion, respectively. The contents of TNF-α and IL-6 in pulmonary tissue and peripheral blood were detected by ELISA. Suramin or saline-pretreated human mononuclear THP-1 cells were treated with 100 ng/mL LPS in vitro. The expression of TNF-α and IL-6 mRNA and the activity of NF-κB were analyzed by quantitative PCR and Western blotting at different time points after LPS treatment, respectively. Results:Compared with the saline group, the TNF-α and IL-6 levels in pulmonary tissue and peripheral blood were significantly reduced in suramin group at 24 h after LPS treatment(all P<0.01); while there was no significant difference at 72 h between two groups(all P>0.05). The expression of TNF-α, IL-6 mRNA and the activity of NF-κB was decreased in suramin group at different time points after LPS treatment. Conclusion:Suramin can protect LPS-induced acute lung injury through down-regulation of systemic and pulmonary pro-inflammatory factors, which may be associated with the inhibition of NF-κB activity.
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Received: 23 March 2015
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苏拉明对脓毒症小鼠肺组织和循环炎症反应的抑制作用
目的:观察苏拉明对脓毒症小鼠肺组织和循环炎症反应的抑制作用,并初步探讨其相关分子生物学机制。方法:①体内实验:将24只雄性C57BL/6小鼠按数字表法分为苏拉明组和生理盐水组,苏拉明组给予静脉注射5 mg/kg苏拉明预处理,生理盐水对照组给予等体积0.9%氯化钠溶液,30 min后采用静脉注射5 mg/kg脂多糖(LPS)建立脓毒症小鼠模型,检测不同时间点肺组织和外周血TNF-α和IL-6水平。②体外实验:苏拉明或生理盐水预处理人单核细胞系THP-1细胞30 min后,用100 ng/mL LPS刺激建立脓毒症细胞模型,于不同时间点收集THP-1细胞,提取RNA,定量PCR检测TNF-α和IL-6表达水平,并分离细胞浆和细胞核蛋白,蛋白质印迹法检测核因子κB(NF-κB)活性。结果:LPS干预后小鼠肺和外周血TNF-α和IL-6水平增加,提示成功建立脓毒症小鼠模型。与生理盐水组比较,苏拉明干预脓毒症小鼠模型作用24 h时小鼠肺组织及外周血TNF-α和IL-6的水平降低(均P<0.01);而苏拉明作用72 h时各组小鼠肺组织及外周血TNF-α和IL-6的水平差异无统计学意义(均P>0.05)。体外实验结果显示:苏拉明预处理减少LPS刺激THP-1细胞后TNF-α和IL-6的表达水平(均P<0.01),苏拉明预处理还减少LPS刺激30 min、60 min和90 min后THP-1细胞NF-κB的活化水平(均P<0.01)。结论:苏拉明可减轻小鼠全身及肺组织炎症反应,在对脓毒症肺损伤模型中具有保护作用,其炎症反应的调控可能与抑制脓毒症单核细胞的过度活化有关。
关键词：
苏拉明/药理学,
肺/损伤,
脓毒症/药物疗法,
肿瘤坏死因子-&alpha,
白细胞介素-6,
NF-&kappa,
B,
疾病模型,
动物
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