摘要
目的:探讨槲皮素防治金黄色葡萄球菌致小鼠肺炎的IKK/NF-κB/IκB炎症信号通路机制。方法:将60只小鼠随机分为阴性对照组(生理盐水)、模型组、阳性对照组(青霉素)及槲皮素50、100、200 mg/kg剂量组,10只/组,每天给药1次,连续3 d。实验第4 d,除阴性对照组外,其余组采用金黄色葡萄球菌气道滴入法建立小鼠感染性肺炎模型,再继续给药3 d。末次药后3 h,小鼠摘眼球取血,采用酶联免疫吸附法(ELISA)测定TNF-α、IL-6及IL-1β含量,然后立即颈椎脱臼处死小鼠,分离肺组织,取肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)进行白细胞分类计数,取左侧肺组织进行病理组织学HE染色检查,取右侧肺组织采用RTPCR及Western blot法检测NF-κB、IKKβ和IκBαmRNA和蛋白表达水平。结果:与阴性对照组比较,模型组BALF中性粒细胞、淋巴细胞、单核细胞计数明显升高,血清TNF-α、IL-6、IL-1β含量明显升高,肺组织炎性病变加重,肺组织NF-κB、IKK mRNA和蛋白表达明显上调,IκBαmRNA和蛋白明显下调。与模型组比较,槲皮素100、200 mg/kg组小鼠BALF中淋巴细胞、单核细胞及中性粒细胞计数明显减少,血清TNF-α、IL-6及IL-1β含量显著下降;槲皮素200 mg/kg组小鼠肺组织炎性病变明显减轻,肺组织NF-κB、IKK mRNA和蛋白表达水平下调,IκBαmRNA和蛋白表达水平上调。结论:槲皮素抑制金黄色葡萄球菌肺炎小鼠炎症反应与其抑制IKK/NF-κB/IκB炎症信号通路有关。
Objective: To investigate the effect of quercetin on mice with pneumonia induced by staphylococcus aureus and its’ mechanism related to IKK/NF-κB/IκB signaling pathway. Methods: 60 mice were randomly divided into the negative control group (normal saline),the model group,the positive control group (penicillin) and quercetin groups (200,100,50 mg/kg),10 mice in each group. Mice were given correspond drugs or saline water once a day for 3 days. On the 4 th day of the experiment,except for the negative control group,mice in other groups were instilled staphylococcus aureus intratracheally to establish the pneumonia model,then the drugs were given for another 3 successive days. 3 hours after the last administration,the blood of mice was taken via pick eyeball method to detect the contents of TNF-α,IL-6 and IL-1β by ELISA. Then mice were sacrificed to separate the lung tissues,BALF was collected to determine the leukocyte differential count.Pathological changes of the left lung tissues were observed by H&E staining. The expression levels of NF-κB,IKK and IκBα mRNA and protein in right lung tissues were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western bolt method. Results:Compared with the negative control group,the numbers of lymphocyte,monocyte and neutrophil in BALF of mice model group were significantly increased,the serum contents of TNF-α,IL-6 and IL-1βin the model group were significantly increased,the inflammatory pathological changes of lung tissues were increased,the expression levels of NF-κB and IKK mRNA and protein in lung tissues were significantly up regulated,the expression level of IκBα mRNA was significantly down regulated. Compared with the model group,the numbers of lymphocyte,monocyte and neutrophil in quercetin groups (100、200 mg/kg) were significantly decreased,the serum contents of TNF-α,IL-6 and IL-1βwere significantly decreased,the inflammatory pathological changes of lung tissues was significantly alleviated in 200 mg/kg quercetin group,the expression levels of NF-κB and IKK mRNA and protein in lung tissues were significantly down regulated,and the expression level of IκBα mRNA was significantly up regulated. Conclusion: Quercetin can inhibit the inflammatory response of mice with pneumonia induced by staphylococcus aureus via inhibiting the IKK/NF-κB/IκB inflammatory signaling pathway.
作者
王婷婷
冷承浩
郭昆鹏
金少举
Wang Tingting;Leng Chenghao;Guo Kunpeng;Jin Shaoju(Basic Medicine Department,Luohe Medical College,Luohe 462002;Tlie second Affiliated Hospital of Luohe Medical College,Luohe 462000;Department of pharmacy,Luohe Medical College,Luohe 462002;Tumor Occurrence and Prevention research innovation team of Henan,Luohe 462002)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第4期53-57,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
漯河市科技创新卷项目(编号:20181000009)
漯河医学高等专科学校校级项目(2015-S-LMC010)
