HMGB1在三叉神经痛中的作用

The role of HMGB1 in trigeminal neuralgia

目的构造大鼠三叉神经痛(TN)模型探索三叉神经节(TG)内高迁移率族蛋白B1(HMGB1)的表达情况及HMGB1对疼痛影响的可能机制。方法采用眶下神经缩窄术构造大鼠TN模型,分为手术组(CCI组)和空白组(Sham组),机械痛阈检测鉴定模型构建是否成功;实时荧光定量PCR(RT-qPCR)及Western blot检测Sham组及CCI组大鼠术侧TG中HMGB1、Toll样受体4(TLR4)、核因子κB(NF-κB)mRNA和蛋白表达量;连续两周每天腹腔注射50 mg/kg HMGB1抑制剂甘草酸(GL),以生理盐水(NS)作为对照,分为CCI组、CCI+NS组、CCI+GL组;RT-qPCR及Western blot检测CCI组、CCI+NS组、CCI+GL组大鼠术侧TG中HMGB1,TLR4、NF-κB mRNA和蛋白表达量。结果大鼠术侧机械阈值持续降低(P<0.05),TN模型构造成功,大鼠眶下神经受到慢性压迫性损伤,术侧TG中的HMGB1、TLR4、NF-κB mRNA及蛋白表达量升高(P<0.05);腹腔注射GL后,术侧TG中的HMGB1、TLR4、NF-κB降低(P<0.05)。结论HMGB1与TN有关,HMGB1可能通过TLR4/NF-κB通路调控TN。

Objective To construct a rat model of trigeminal neuralgia(TN)to explore the expression of high-mobility group box-1(HMGB1)in the trigeminal ganglion(TG)and the possible mechanism of HMGB1's effect on pain.Methods TN model was constructed by infraorbital nerve constriction and divided into operation group(CCI group)and Sham group,and the success of the model construction was determined through mechanical pain threshold assessment.Real time fluorescence quantitative PCR(RT-qPCR)and Western blot were used to detect high mobility group protein B1(HMGB1),Toll receptor 4(TLR4),and Nuclear Factor Kappa B(NF-κB)mRNA and protein expression in the ipsilateral trigeminal ganglion(TG)of the Sham and CCI rats.50 mg/kg HMGB1 inhibitor glycyrrhizin(GL)was injected intraperitoneally every day for two weeks,and normal saline(NS)was used as control.The patients were divided into CCI group,CCI+NS group and CCI+GL group.HMGB1,TLR4,and NF-κB mRNA and protein expression in the ipsilateral trigeminal ganglion(TG)were detected by RT-qPCR and Western blot in CCI group,CCI+NS group,and CCI+GL group.Results The mechanical threshold on the operated side of the rat continued to decrease(P<0.05),and mechanical pain threshold identification model was successfully constructed.After chronic compressive injury to the infraorbital nerve in rats,HMGB1,TLR4,and NF-κB mRNA and protein expression in TG on the operated side increased(P<0.05);After administration of HMGB1 inhibitor Glcyrrhizin,HMGB1,TLR4,NF-κB showed a decrease(P<0.05).Conclusion HMGB1 is associated with TN,and HMGB1 may be involved in the pathogenesis of TN through TLR4/NF-κB signaling pathway.