上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2018, Vol. 38 ›› Issue (8): 888-.doi: 10.3969/j.issn.1674-8115.2018.08.006

• 论著·基础研究 • 上一篇    下一篇

Toll样受体纳米抑制剂 P12对急性肺损伤小鼠肺部炎症的调节作用

高炜，孙立亚，王璐，王琨，李强，杨红   

  1. 上海交通大学附属第一人民医院呼吸与危重症科，上海 201620
  • 出版日期:2018-08-28 发布日期:2018-09-11
  • 通讯作者: 杨红，电子信箱：hongyang36@gmail.com。
  • 作者简介:高炜（1988—），女，博士生；电子信箱： grace19881118@126.com。
  • 基金资助:
    国家自然科学基金（ 81770070）；上海高效特聘教授（东方学者）岗位计划（ TP2016014）；上海市教育委员会高峰高原学科建设计划（ 20171923）

Effect of Toll-like receptor nano-inhibitor P12 on pulmonary inflammation in acute lung injury mice

GAO Wei, SUN Li-ya, WANG Lu, WANG Kun, LI Qiang, YANG Hong   

  1. Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
  • Online:2018-08-28 Published:2018-09-11
  • Supported by:
    National Natural Science Foundation of China, 81770070; Shanghai Eastern Scholar Program (TP2016014); Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Support, 20171923

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摘要： 目的 ·探讨 Toll样受体纳米抑制剂 P12对脂多糖（ lipopolysaccharides，LPS）诱导的 THP-1来源的巨噬细胞及急性肺损伤（acute lung injury，ALI）模型小鼠的调节作用。方法 ·体外培养 THP-1细胞，诱导分化为巨噬细胞，以 LPS及 P12处理 24 h后检测培养基中促炎因子分泌水平。选用 6～ 8周 C57BL/6野生型小鼠，随机分为 PBS对照组、 LPS造模组及 LPS+P12干预组，收集小鼠肺泡灌洗液（ bronchial alveolar lavage fluid，BALF）及肺组织，以细胞总计数、分类计数及酶联免疫吸附法检测各组小鼠肺部炎症反应程度；肺组织切片行苏木精 -伊红染色，镜下观察 ALI小鼠肺部病理改变并对其进行损伤评分。结果 ·体外研究显示， P12可明显抑制 LPS诱导的 THP-1来源巨噬细胞促炎因子分泌。体内实验表明， P12干预可有效缓解 ALI小鼠肺部急性炎症损伤程度，包括减少 BALF总细胞数和中性粒细胞数、下调 BALF炎性趋化因子（ KC、CCL-2）的表达、降低肺组织损伤病理评分等。结论 ·抗炎纳米药剂 P12可显著抑制 LPS诱导的 THP-1来源巨噬细胞炎症因子释放并有效缓解 ALI小鼠肺部炎症损伤程度；该结果可为 ALI的早期临床救治提供全新思路。

关键词: 急性肺损伤, Toll样受体, 多靶点抗炎活性, 纳米抑制剂, 纳米粒子

Abstract:

Objective · To investigate the effect of the Toll-like receptor (TLR) nano-inhibitor P12 on THP-1 derived macrophages and acute lung injury (ALI) momodel inducedlipopolysaccharides (LPS). Methods · In in vitro experiments, THP-1 cells were differentiated into macrophage-like cells and then treated with LPS in the absence and presence of P12.After 24 h incubation, medium was collected to quantify the secretion of pro-inflammatory cytokines using enzyme-linked immunosorbent assay (ELISA). Six-to eight-week-old C57BL/6 mice were randomly divided into three groups, i.e. PBS control, LPS challenge and P12 pretreatment plus LPS. The bronchial alveolar lavage fluid (BALF) and lung tissue of each mowere collected, and the acute inflammatory response within lung was evaluatedtotal cell counts, differential cell counts and ELISA. Pathological injury scores in ALI mice were assessed with hematoxylin and eosin (H-E) staining of lung tissue sections under microscope. Results · In THP-1 derived macrophages, P12 significantly inhibited LPS-induced inflammatory cytokine production. In the LPS-induced ALI momodel, P12 significantly attenuated the acute inflammatory response and alveolar damage in lung, including reducing the number of total cells and neutrophils in BALF, decreasing the of chemokine production (KC and CCL-2), and lowering lung injury scores. Conclusion · P12 exhibits potent anti-inflammatory activity in THP-1 derived macrophages and in the LPS-induced ALI momodel, providing new concepts for the early treatment of ALI.

Key words: acute lung injury (ALI), Toll-likereceptor (TLR), multi-target anti-inflammatory activity, nano-inhibitor, nanoparticle

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