A系统转运体-1在慢性胰腺炎大鼠持续性疼痛中的作用研究

Role of system A transporter-I in the modulation of persistent pain in a rat model of chronic pancreatitis

目的 研究A系统转运体-1（SAT1）在慢性胰腺炎（CP）大鼠持续性疼痛中的作用,探讨CP疼痛的神经病理机制.方法 胆胰管内逆行灌注2％三硝基苯磺酸（TNBS）诱导CP大鼠模型,分别通过胰腺病理学和大鼠对von-Frey探针刺激腹部的敏感性来评估胰腺炎的严重程度及痛觉过敏情况;采用Western blot法检测大鼠胸髓背角中SAT1的表达;鞘内注射MeAIB（SAT1竞争性抑制剂）后,评估模型大鼠腹部机械性痛觉过敏的变化.结果 TNBS成功诱导了大鼠CP,模型大鼠出现持续的腹部机械性痛觉过敏,其胸髓背角中SAT1蛋白表达明显上调（P〈0.05）,鞘内注射MeAIB显著抑制了CP模型大鼠的腹部机械性痛觉过敏（P〈0.05）.结论 SAT1可能在CP的持续性疼痛中发挥促进作用,抑制SAT1的活性或表达可能成为临床缓解CP患者疼痛的治疗靶点.

Objective To investigate the effect of system A transporter-1 （SAT1） on persistent pain in the rat model of chronic pancreatitis（CP） and to explore the neuropathic mechanism involved in this type of pain. Methods CP was induced by an intraductal perfusion of 2% trinitrobenzene sulfonic acid （TNBS）. The severity of CP was assessed by pancreatic histology. Abdominal hyperalgesia, based on the expression of mechanical sensitivity evoked by von-Frey filaments, was evaluated. The expression of SAT1 in spinal dorsal horn was evaluated by Western blotting. In order to clarify the role of SAT1 in pain in CP, we intrathecally injected the rats with MeAIB （ a competitive inhibitor of SAT1 ）. Then we evaluated its effects on the abdominal mechanical hyperalgesia in the rats with CP. Results TNBS induced CP successfully. Rats subjected to TNBS injections had persistent and enhanced sensitivity to mechanical stimulation of the abdomen. The expression of SAT1 was up-regulated in CP rats （ P 〈 0.05 ）. Intrathecal injection of MeAIB significantly inhibited the mechanical hyperalgesia （ P 〈 0.05 ）. Conclusion SAT1 in thoracic spinal dorsal cord exerts a pain promoting effect on persistent pain in CP. Inhibition of SATI activity or expression may be a therapeutic target for pain remission in patients with CP.