摘要
目的:探索诺米林(Nomilin)对克雷伯菌(Klebsiella)老年肺炎大鼠炎症反应的影响。方法:克雷伯菌感染诱导肺炎模型。大鼠随机分为5组:健康对照组(Ctrl),克雷伯菌肺炎模型组,诺米林(10、25、50 mg/kg BW)治疗组。苏木素-伊红(HE)染色观察肺部组织病变。脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色检测肺部组织细胞凋亡。酶联免疫吸附实验(ELISA)检测肺部组织白细胞介素(IL)-6、IL-1β和肿瘤坏死因子(TNF-α)水平。流式细胞仪检测外周血CD14阳性细胞比例。蛋白印迹检测肺部组织CD14、TLR4、NF-κB P65和p-P65的蛋白水平。结果:诺米林可改善克雷伯菌老年肺炎大鼠肺部组织病变。克雷伯菌显著诱导老年大鼠肺脏组织细胞凋亡,而诺米林可剂量依赖性地抑制克雷伯菌诱导的肺脏细胞凋亡(P<0. 01)。克雷伯菌显著提高老年大鼠炎症因子IL-6、IL-1β和TNF-α水平,而诺米林可有效抑制克雷伯菌诱导的炎症因子IL-6、IL-1β和TNF-α水平的升高(P<0. 01)。克雷伯菌显著提高老年大鼠外周血中CD14阳性细胞数比例,诺米林可有效抑制克雷伯菌诱导的外周血中CD14阳性细胞数比例的上升(P<0. 01),且呈剂量依赖性。克雷伯菌显著提高老年大鼠CD14和TLR4表达及p-P65/P65蛋白比值,诺米林可有效抑制克雷伯菌诱导的CD14和TLR4表达及p-P65/P65蛋白比值的升高(P<0. 01),且呈剂量依赖性。结论:诺米林可通过抑制TLR4/NF-κB炎症通路的活化缓解克雷伯菌老年肺炎大鼠肺部组织病变、细胞凋亡及炎症反应。
Objective:To explore the effects of Nomilin on inflammatory response in the Klebsiella-induced geriatric pneumonia rats.Methods:The model of pneumonia was induced by Klebsiella infections.Rats were randomly divided into five groups,including control group,Klebsiella pneumoniae model group and Nomilin(10,25,50 mg/kg BW)treatment groups.The pathological changes of lung tissues were observed by hematoxylin-eosin(HE)staining.The apoptosis of lung tissues was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP nick labeling(TUNEL).The levels of interleukin(IL)-6,IL-1βand tumor necrosis factorα(TNF-α)in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).The content of CD14 in peripheral blood was detected by flow cytometry.The protein levels of CD14,TLR4,NF-κB P65 and p-P65 in lung tissues were tested by Western blot.Results:The pathological changes of lung tissues were ameliorated by Nomilin.The apoptosis of lung tissues in model group was higher than control group(P<0.01).The apoptosis of lung tissues in Nomilin(10,25,50 mg/kg BW)group was lower than model group(P<0.01).The levels of IL-6,IL-1βand TNF-αin model group were higher than control group(P<0.01).Compared with model group,the levels of IL-6,IL-1βand TNF-αin Nomilin(10,25,50 mg/kg BW)group were reduced(P<0.01).The rate of CD14 positive cell of the peripheral blood in model group was higher than control group(P<0.01).Compared with model group,the rate of CD14 positive cell of the peripheral blood in Nomilin(10,25,50 mg/kg BW)group was decreased(P<0.01).The expression of CD14 and TLR4 and rate of p-P65/P65 in model group were higher than control group(P<0.01).Compared with model group,the expression of CD14 and TLR4 and rate of p-P65/P65 in Nomilin(10,25,50 mg/kg BW)group were reduced(P<0.01).Conclusion:Nomilin alleviates the pathological changes,apoptosis and inflammatory response by inhibiting activation of LR4/NF-κB pathway in Klebsiella-induced geriatric pneumonia rats.
作者
刘泽明
孙颖
高玉春
龙怀聪
雷霆
杜恒健
LIU Ze-Ming;SUN Ying;GAO Yu-Chun;LONG Huai-Cong;LEI Ting;DU Heng-Jian(Department of Infectious Disease,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2019年第8期970-975,共6页
Chinese Journal of Immunology
基金
四川省科技厅课题项目(2019YFS0309)
四川省干部保健课题项目(2018210)
