上海交通大学学报(医学版) ›› 2017, Vol. 37 ›› Issue (7): 936-.doi: 10.3969/j.issn.1674-8115.2017.07.009?

• 论著(基础研究) • 上一篇    下一篇

雌激素调控去势小鼠疼痛的炎症机制

王芷,宋小星,张富军   

  1. 上海交通大学  医学院附属瑞金医院麻醉科,上海 200025
  • 出版日期:2017-07-28 发布日期:2017-08-25
  • 通讯作者: ?张富军,电子信箱:fujunzhang1964@163.com
  • 作者简介:王芷(1990—),男,硕士生;电子信箱:sjtuwz@outlook.com
  • 基金资助:
     国家自然科学基金(81400910)

Inflammatory mechanism of estrogen in the pain modulation of ovariectomized mice#br#

WANG Zhi, SONG Xiao-xing, ZHANG Fu-jun   

  1. Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2017-07-28 Published:2017-08-25
  • Supported by:
    National Natural Science Foundation of China, 81400910

摘要:  目的 · 通过建立去势小鼠模型并给予外源性雌激素补充治疗,探索雌激素调控去势小鼠疼痛的炎症机制。方法 · 24 只 12 周 龄 C57BL/6J 雌性小鼠随机分为 3 组:假手术组(S 组),手术 + 安慰剂对照组(P 组),手术 + 雌激素替代治疗组(E 组)。术后 1 周 给予雌激素替代治疗,为期4 周。分别在术前1 日、术后3 日及术后1、2、3、4、5 周检测小鼠基础痛阈,包括机械痛阈缩足阈值 (PWT)和热板痛阈缩足潜伏期(PWL);术后 3 日及 5 周检测小鼠血清炎症因子水平,包括 IL-1β、IL-6、TNF-α;术后 5 周取小鼠脊 髓腰膨大,Western blotting 分析 p38 表达含量。结果 · 去势小鼠术后基础痛阈均较 S 组低,PWT、PWL 分别在术后第 1 周、术后第 3 日起与 S 组差异有统计学意义(P<0.01)。术后第 3 日,E 组、P 组炎症因子水平均较 S 组高,差异具有统计学意义(P<0.01)。术后 第 5 周,P 组 p38 表达高于 S 组,差异具有统计学意义(P<0.01)。给予雌激素补充治疗后,术后第4、5 周,E 组 PWT、PWL 均略 有提高,与 P 组差异具有统计学意义(P<0.01)。术后第 5 周 E 组炎症因子表达降低,与 P 组差异具有统计学意义(P<0.01),但也 仍然显著高于 S 组(P<0.01)。术后第 5 周 E 组 p38 表达含量降低但仍高于 S 组,与 P 组差异具有统计学意义(P<0.01),而与 S 组 比较差异已无统计学意义(P>0.05)。 结论 · 雌激素可能通过 p38 MAPK 通路降低炎症因子水平,发挥对去势小鼠疼痛的调控作用。

关键词: &ensp, 雌激素, 疼痛, 炎症, p38

Abstract:

Objective · Giving the ovariectomized (OVX) mice exogenous estrogen replace therapy (ERT) so as to explore the inflammatory mechanism of estrogen in the pain modulation of OVX mice.  Methods · Twenty-four 12-week-old female C57BL/6J mice were randomized into three groups: sham group (S), ovariectomy+placebo group (P), ovariectomy+estrogen group (E). The ERT began from one week after OVX and last for four weeks. Paw withdraw threshold (PWT) and paw withdraw latency (PWL) were measured at one day before OVX, and three days, one week, two weeks, three weeks, four weeks and five weeks after OVX. Concentrations of inflammatory cytokines in serum were measured at three days and five weeks postoperatively. Five weeks after operation, the lumbar intumescentia of spinal cord was taken and the expression of p38 was analyzed by Western blotting.  Results · All the OVX mice’s PWTs or PWLs were decreased after operation compared with non-operation mice; PWTs and PWLs were significantly different from group S separately from one week and three days after OVX (P<0.01). The inflammatory cytokines of OVX mice were significantly higher than group S (both P<0.01) at three days after OVX. Western blotting results showed that the p38 of group P was significantly higher than that of group S after five weeks postoperatively (P<0.01). By receiving ERT, both PWTs and PWLs of group E increased slightly and were significantly different from group S (P<0.01) at four and five weeks after OVX. At five weeks after OVX, inflammatory cytokines of group E were significantly lower than group P (P<0.01) but still much higher than group S (P<0.01). Meanwhile the content of p38 in group E was less than that in group P (P<0.01). The p38 in group E was still more than group S, however it was no longer significantly different from group S (P>0.05).  Conclusion · Estrogen may reduce concentrations of inflammatory cytokines through the p38 MAPK pathway and plays an important role in the pain modulation of OVX mice.

Key words: estrogen, pain, inflammation, p38