TLR7通过NF-κB炎症通路调控ION-CCI模型大鼠三叉神经痛的机制

Mechanism of TLR7 regulating trigeminal neuralgia in ION-CCI model rats through NF-κB inflammatory pathway

目的研究Toll样受体7(TLR7)在SD大鼠三叉神经疼痛中的作用,并初步探讨TLR7在疼痛过程中通过激活核因子-κB(NF-κB)通路介导相关炎症因子的作用机制。方法采用眶下神经缩窄术(ION-CCI)建立大鼠三叉神经痛(TN)模型。通过实时荧光定量聚合酶链反应(qRT-PCR)及免疫印迹法(Western blot)检测三叉神经节(TG)内TLR7表达变化。经灌胃给药方式向ION-CCI大鼠给予TLR7抑制剂羟基氯喹(HCQ),检测抑制后TG内TLR7及其下游信号通路NF-κB亚基p65、p-p65及炎症因子TNF-α、IL-1β表达的变化。结果结扎眶下神经所致的三叉神经损伤后,大鼠TG内的TLR7表达增加(P<0.05)。在给予TLR7抑制剂后,大鼠TG内TLR7和TNF-α、IL-1β表达降低,并且p65核内移位和磷酸化减弱,NF-κB信号通路激活被抑制,IONCCI诱导的雄性SD大鼠的机械疼痛得到缓解(P<0.05)。结论TG内TLR7通过激活初级感觉神经元中的NF-κB介导炎症因子TNF-α、IL-1β的表达参与调控神经病理性疼痛。

Objective To study the role of Toll-like receptor 7(TLR7)in trigeminal nerve pain in SD rats,and to explore the mechanism of TLR7 mediating related inflammatory factors through the activation of NF-κB pathway during the process of pain.Methods The rat model of trigeminal neuralgia(TN)was established by infraorbital nerve constriction injury(ION-CCI).The expression of TLR7 in trigeminal ganglion(TG)was detected by qRT-PCR and Western blot.Hydroxychloroquine(HCQ),an inhibitor of TLR7,was given to ION-CCI rats by intragastric administration.The expression of TLR7 and its downstream signal pathway NF-κB subunit p65,p-p65 and inflammatory factors(TNF-α,IL-1β)in TG were detected.Results After trigeminal nerve injury induced by ligation of infraorbital nerve,the expression of TLR7 in TG of rats significantly increased.After administration of TLR7 inhibitor,the expression of TLR7,TNF-α and IL-1β in TG decreased,the translocation and phosphorylation of p65 nucleus decreased,the activation of NF-κB signal pathway was inhibited,and the mechanical pain induced by ION-CCI was relieved in male SD rats.Conclusion TLR7 in TG regulates neuropathic pain by activating NF-κB signal pathway in primary sensory neurons and mediating the expression of inflammatory cytokines TNF-α and IL-1β.