上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2017, Vol. 37 ›› Issue (12): 1588-.doi: 10.3969/j.issn.1674-8115.2017.12.002

• 论著（基础研究） • 上一篇    下一篇

外源性阻断 RAGE 效应对糖尿病小鼠创面中巨噬细胞浸润的影响

#br# 王齐1*，曹晓赞 2*，朱冠娅 2，宋菲 2，陆树良 2，牛轶雯 2   

  1. 1.上海交通大学医学院附属第九人民医院急诊科，上海 200011；2.上海交通大学医学院附属瑞金医院，上海烧伤研究所，上海 200025
  • 出版日期:2017-12-28 发布日期:2018-01-10
  • 通讯作者: 牛轶雯，电子信箱：13636489036@163.com
  • 作者简介:?王 齐（1990—），女，硕士生；电子信箱：15021556851@163.com。曹晓赞（1983—），女，主管技师，硕士；电子信箱：515965467@qq.com。* 为共同第一作者。
  • 基金资助:
     国家自然科学基金面上项目（81272111, 81671917）

Effect of blocking RAGE on macrophage infiltration of diabetic wound healing

WANG Qi1*, CAO Xiao-zan2*, ZHU Guan-ya2, SONG Fei2，LU Shu-liang2, NIU Yi-wen2   

  1. 1. Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 2. Shanghai Burn Institute, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2017-12-28 Published:2018-01-10
  • Supported by:
    （National Natural Science Foundation of China, 81272111, 81671917

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摘要： [ 摘要 ] 目的 · 通过外源性阻断糖基化终末产物受体（RAGE）后，观察 RAGE 效应对糖尿病小鼠创面愈合过程中巨噬细胞浸润的影
响。方法 · 96 只雄性 8 周龄 C57BL/6J 小鼠随机分成糖尿病组（n=72）和正常对照组（n=24）。多次小剂量链脲佐菌素腹腔注射诱导糖尿病小鼠模型，并用灭菌 9 mm 直径环钻于小鼠背部制造全层皮肤缺损创面模型。伤后正常对照组创面局部用 0.9% 氯化钠溶液（N组）；糖尿病组再随机分成 3 组，糖尿病空白对照组（C 组）创面局部外用 0.9% 氯化钠溶液，糖尿病 IgG 对照组（I 组）创面局部外用兔 IgG，糖尿病 RAGE 干预组（R 组）创面局部外用 RAGE 抗体。再于伤后第 3 日和第 7 日，给予相同处理。通过大体评估创面愈合情况；于伤后第 1、3、7 日切取创缘皮肤样本，免疫组织化学染色标记并计数创面中巨噬细胞数量，透射电子显微镜下观察巨噬细胞超微结构。结果 · ①伤后第 14 日，R 组创面愈合面积百分比显著高于 C 组和 I 组（均 P=0.000）。②伤后第 1 日，N 组和 R 组CD68+ 巨噬细胞数均显著多于 C 组（均 P=0.000）；伤后第 14 日，N 组和 R 组巨噬细胞数均显著少于 C 组（均 P=0.000）。③电子显微镜下对比创面组织的巨噬细胞形态及结构，存在明显不同。结论 · 糖尿病创面环境中，RAGE 效应与创面巨噬细胞浸润数量及形态的异常密切相关，从而参与了糖尿病创面的难愈。

关键词:  糖尿病, 巨噬细胞, 糖基化终末产物受体, 创面愈合

Abstract:

[Abstract] Objective · To investigate the influence of blocking receptor for advanced glycation end products (RAGE) on macrophages infiltration in
diabetic wound healing. Methods · Ninety-six male C57BL/6J mice (8-week-old) were divided into diabetic group (n=72) and normal group (n=24)
randomly. Diabetic mice were induced by streptozocin multiple intraperitoneal injection. One full-thickness excisional wound (diameter of 9 mm) was
created by a sterilized punch. Diabetic mice were divided into 3 groups in which different topical treatments were applied to the wounds. Anti-RAGE
antibody were applied in group R, rabbit IgG applied in group I, normal saline applied in group C. Normal mice were applied with saline topically (group N).
All treatments were repeated on day 3 and day 7 after wounded. The wound healing conditions were observed. The wound and surrounding tissues from
animals in each group were excised on day 1, 3, and 7 after wounded. Immunohistochemistry was utilized to investigate the changes of macrophages
infiltration in quantity. Macrophages were also analyzed with respect to morphology by transmission electron microscopy (TEM). Results · ① The
wound closure ratio of group R was higher than those of group C and group I on day 14 after being wounded (P=0.000). ② On day 1, the numbers of
macrophages in group R and group N were both bigger than those of group C and group I, but smaller on day 14 (P=0.000). ③ The morphological
characters of macrophages also existed great differences under TEM. Conclusion · Number and morphology of macrophages are both abnormal in
diabetic wound in a RAGE pathway depending manner. Based on macrophages, it suggests that impaired healing of diabetic wound is closely related to
RAGE pathway.

Key words: diabetes mellitus, macrophage, receptor for advanced glycation end products, wound healing