印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎

孙慧; 田湉; 熊廷蓉; 邹全明; 张笑恺; 杨宪; 王于

doi:10.16016/j.2097-0927.202312104

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印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎

基础医学 | 更新时间：2026-01-09

- 印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎
- Nimbolide targets RNF114 in treatment of mouse model of acute pneumonia caused by Staphylococcus aureus
- 陆军军医大学学报 2024年46卷第12期页码：1353-1360
- 作者机构：
  
  1.401331 重庆，重庆师范大学: 生命科学学院活性物质生物技术教育部工程研究中心
  2.400038 重庆，陆军军医大学药学与检验医学系微生物与生化药学教研室，国家免疫生物制品工程技术研究中心
  3.050081 河北石家庄，陆军军医大学士官学校基础部
- 作者简介：
  
  [杨宪, E-mail: 464997677@qq.com YANG Xian, E-mail: 464997677@qq.com
  [王于, E-mail: xiaoyu027111@163.com WANG Yu, E-mail: xiaoyu027111@163.com
- 基金信息：
  
  国家自然科学基金(82201942)
- DOI：10.16016/j.2097-0927.202312104
  中图分类号： R282.71;R378.11;R563.1
- 收稿：2023-12-21，
  
  修回：2024-03-21，
  
  纸质出版：2024-06-30
- 稿件说明：
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孙慧, 田湉, 熊廷蓉, 等. 印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎[J]. 陆军军医大学学报, 2024,46(12):1353-1360.

Hui SUN, Tian TIAN, Tingrong XIONG, et al. Nimbolide targets RNF114 in treatment of mouse model of acute pneumonia caused by Staphylococcus aureus[J]. Journal of Army Medical University, 2024, 46(12): 1353-1360.
孙慧, 田湉, 熊廷蓉, 等. 印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎[J]. 陆军军医大学学报, 2024,46(12):1353-1360. DOI： 10.16016/j.2097-0927.202312104.

Hui SUN, Tian TIAN, Tingrong XIONG, et al. Nimbolide targets RNF114 in treatment of mouse model of acute pneumonia caused by Staphylococcus aureus[J]. Journal of Army Medical University, 2024, 46(12): 1353-1360. DOI： 10.16016/j.2097-0927.202312104.

摘要

目的

探究印苦楝内酯(nimbolide，NIM)治疗金黄色葡萄球菌急性肺炎作用机制。

方法

通过气管插管构建小鼠金葡菌急性肺炎模型，NIM治疗后，观察小鼠生存率差异，平板培养分析肺部荷菌量变化，ELISA检测肺组织炎性细胞因子表达差异；ELISA及Western Blot检测腹腔原代巨噬细胞感染金葡菌后，NIM对炎症细胞因子的表达水平及炎症通路激活的影响；慢病毒shRNA敲低原代腹腔巨噬细胞RNF114蛋白水平，通过ELISA及Western Blot探究NIM是否通过RNF114抑制炎症反应。

结果

金葡菌感染小鼠肺部后可导致急性死亡，NIM显著提高了小鼠生存率，下调小鼠肺部炎症细胞因子水平，但短期内不影响金葡菌肺部定植；巨噬细胞感染结果表明，NIM可能通过调控RNF114功能，下调ERK的磷酸化水平抑制MAPK通路激活，进而抑制炎症细胞因子的表达。

结论

NIM可能通过调控巨噬细胞RNF114功能，抑制MAPK通路激活进而抑制小鼠肺部炎症细胞因子的表达，最终抑制金葡菌急性肺部高炎症导致的小鼠死亡。

Abstract

Objective

To explore the mechanism which drives nimbolide (NIM) in treating acute pneumonia caused by

Staphylococcus aureus

(

S. auteus

Methods

A mouse model of acute pneumonia caused by

S. auteus

was constructed through endotracheal intubation. After NIM treatment

the survival rate was observed

the amount of bacteria in the lung was tested by plate culture

and the expression of inflammatory cytokines in the lung tissues was detected with ELISA. After primary cultured peritoneal macrophages (PM) were infect

ed with

S. auteus

the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting

respectively. The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.

Results

Acute infection of

S. auteus

in the lung could cause acute death in the mice

while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung. However

it had no effect on the lung colonization of

S. auteus

in the short term. The results of

in vitro

experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK

inhibit the activation of MAPK pathway

and thus suppress the expression of inflammatory cytokines.

Conclusion

NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114

and thus suppress the expression of inflammatory cytokines in the lung

and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by

S. auteus

关键词

Keywords

references

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