Abstract: Objective Based on the HMGB1 / TLR4 / MyD88 signaling pathway, to explore the effect of sulforaphane on chronic mechanical pain in rats with endometriosis ( EMs) . Method The EMs model was constructed by autologous endometrial tissue transplantation in rats. The rats were divided into sham operation group ( sham group) , EMs group, sulforaphane low-dose group (5 mg / kg) , sulforaphane high-dose group ( 15 mg / kg) , HMGB1 inhibitor group ( EP group) , and TLR4 inhibitor group ( TAK-242 group) . The pain threshold of rats was detected by an electronic pain meter; the levels of HMGB1, TNFα, IL-6 and IL-10 in rat serum were detected by ELISA; the protein levels of HMGB1, TLR4, MyD88 and TRPV1 in ectopic endometrial tissue were detected by Western blot. Result Compared with the Sham group, the paw withdrawal threshold ( PWT) of the EMs group was lower (P<0. 05) ; the levels of serum HMGB1, TNF-α, IL-6 and IL-10 were higher ( P < 0. 05) ; the expression of HMGB1, TLR4, MyD88 and TRPV1 proteins in ectopic endometrial tissue was increased (P<0. 05) . Compared with the EMs group, low and high doses of sulforaphane, HMGB1 inhibitor, and TLR4 inhibitor could increase PWT of rat and reduce levels of serum HMGB1, TNF-α, IL-6 and IL-10, and reduce expression of HMGB1, TLR4, MyD88 and TRPV1 proteins in ectopic endometrial tissue ( P < 0. 05) . Conclusion Sulforaphane can reduce the mechanical pain caused by EMs by inhibiting the HMGB1 / TLR4 / MyD88 signaling pathway.

Key words: sulforaphane, HMGB1 / TLR4 / MyD88 signaling pathway, endometriosis, inflammatory response, pain

摘要： 目的 基于 HMGB1 / TLR4 / MyD88 信号通路探讨萝卜硫素对子宫内膜异位症( EMs) 大鼠慢性机械性疼痛的减轻作用。 方法 通过大鼠自体子宫内膜组织移植构建 EMs 模型。 将大鼠分为假手术组( Sham 组) 、EMs 组、萝卜硫素低剂量组(5 mg / kg) 、萝卜硫素高剂量组( 15 mg / kg) 、HMGB1 抑制剂组( EP 组) 和 TLR4 抑制剂组( TAK-242组) 。 通过电子测痛仪检测大鼠痛阈情况;通过ELISA法检测大鼠血清中HMGB1、 TNF-α、 IL-6 和 IL-10 水平;Western blot 检测异位子宫内膜组织 HMGB1、TLR4、MyD88 和 TRPV1 蛋白水平。 结果 与 Sham 组相比,EMs 组大鼠机械痛阈值( PWT)降低(P <0. 05) ;血清中 HMGB1、TNF-α、IL-6 和 IL-10 水平升高( P< 0. 05) ;异位子宫内膜组织中 HMGB1、TLR4、MyD88 和 TRPV1 蛋白表达升高(P<0. 05) 。 与 EMs 组相比,低、高剂量萝卜硫素及 HMGB1 抑制剂和 TLR4 抑制剂均能够升高大鼠 PWT,降低血清中 HMGB1、TNF-α、IL-6 和 IL-10 水平;减少异位子宫内膜组织中 HMGB1、TLR4、MyD88 和 TRPV1 蛋白表达(P< 0. 05) 。 结论 萝卜硫素能够通过抑制 HMGB1 / TLR4 / MyD88 信号通路来减轻 EMs 引起的机械性疼痛。

关键词: 萝卜硫素, HMGB1 / TLR4 / MyD88 信号通路, 子宫内膜异位症, 炎性反应, 疼痛