摘要
目的通过体外细胞学实验和体内动物实验来研究奈诺沙星是否对脂多糖(LPS)诱导的炎性反应具有调控作用。方法①体外细胞学实验检测奈诺沙星对LPS诱导小鼠单核巨噬细胞RAW264.7产生炎性反应的调控作用。RAW264.7细胞液中先加入奈诺沙星,后加入LPS,在不同时间点收集奈诺沙星+LPS组和LPS组等各组细胞上清液,酶联免疫吸附测定(ELISA)方法检测白介素(IL)-6、IL-10以及肿瘤坏死因子(TNF)-α等细胞因子的含量;②低剂量LPS诱导小鼠炎性反应及奈诺沙星干预实验。小鼠先腹腔注射奈诺沙星再注射低剂量LPS(5mg/kg),ELISA方法检测小鼠血清中IL-6、IL-10以及TNF-α等细胞因子的含量;③奈诺沙星对注射高剂量LPS小鼠保护作用的实验:小鼠腹腔注射高剂量的LPS(12.5mg/kg),2h后开始腹腔注射奈诺沙星40mg/kg,1次/12h,记录0~72h实验组和对照组小鼠的死亡率。结果①体外细胞学实验显示奈诺沙星对LPS诱导RAW264.7产生的炎性反应有抑制作用,表现为奈诺沙星抑制IL-6、TNF-α等促炎因子的分泌,促进IL-10等抑炎因子的分泌;②体内动物实验结果显示奈诺沙星对低剂量LPS诱导小鼠的炎性反应也有抑制作用;③奈诺沙星能降低因高剂量LPS引起严重内毒素血症小鼠的死亡率。奈诺沙星+LPS组总体死亡率为0/5,而LPS组总体死亡率为3/5。结论奈诺沙星对宿主感染LPS具有免疫调节作用,可以抑制宿主产生的过度免疫反应,对宿主具有保护作用。
Objective To study the immunomodulatory effect of nemonoxacin on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro.Methods The modulation of nemonoxacin on LPS-induced inflammation was investigated with mice macrophage RAW264.7 in vitro.Nemonoxacin was added to RAW264.7 cell suspension,then LPS was added to the mixture.Then the supernatant was collected at designated time points from the cell culture with LPS + nemonoxacin mixture and that with LPS alone,respectively.The level of IL-6,IL-10 and TNF-α was determined by ELISA.The effect of nemonoxacin on LPS-induced mice inflammation was also studied in vivo.Mice were injected with nemonoxacin,then injected with low doses of LPS (5 mg/ kg). The level of IL-6,IL-10 and TNF-α was detected by ELISA as well.Mice were also challenged with high dose of LPS (12.5 mg/ kg) by intra-abdominal injection,followed by injection of nemonoxacin 40 mg/kg q12 h,2 hours later.The mortality was recorded from 0 h to72 h in the experiment group and control group.Results The in vitro cytological study showed that nemonoxacin had inhibitory effect on LPS-induced inflammation in mice macrophage RAW264.7,which was evidenced by the fact that nemonoxacin significantly reduced production of IL-6 and TNF-α after LPS challenge,but significantly increased IL-10 production.Similar effects were observed in mice experiment that nemonoxacin also had inhibitory effect on mice inflammation induced by low dose of LPS.Nemonoxacin reduced mice mortality after mice were challenged with high dose of LPS (12.5 mg/kg). The overall mortality was 0 in the mice treated with LPS + nemonoxacin and 60% in the mice treated with LPS alone. Conclusions Nemonoxacin had immunomodulatory effect on LPS-induced inflammation.Nemonoxacin can inhibit the excessive immune reaction and so have protective effect on host.
作者
赵旭
李鑫
张菁
郭蓓宁
ZHAO Xu;LI Xin;ZHANG Jing;GUO Beining(Institute of Antibiotics,Huashan Hospital,Fudan University,Key Laboratory of Clinical Pharmacology of Antibiotics,National Health Commission,Shanghai 200040,China)
出处
《中国感染与化疗杂志》
CAS
CSCD
北大核心
2019年第4期351-356,共6页
Chinese Journal of Infection and Chemotherapy
关键词
奈诺沙星
脂多糖
细胞因子
免疫调控
nemonoxacin
lipopolysaccharide
cytokine
immunomodulatory effect
