胱硫醚-β-合成酶参与慢性压迫性损伤大鼠神经病理性痛的作用

Role of CBS in neuropathic pain of rats with chronic constriction injury

目的评价胱硫醚-β-合成酶(CBS)在大鼠神经病理性痛形成中的作用。方法 SPF级健康雄性SD大鼠36只,180～200 g,5～6周龄,采用随机数字表法分为3组(n=12):神经病理性痛组(CCI组)、CBS抑制剂组(CCI+AOAA组)及假手术组(Sham组);鞘内成功置管后第3天,建立大鼠CCI模型(坐骨神经缩窄性损伤法);术后1 d开始连续鞘内注射14 d(每天1次):CCI+AOAA组鞘内注射AOAA(10μg/kg)10μL+生理盐水10μL,Sham和14 d测定热痛阈和机械痛阈。术后7、14 d处死大鼠,取脊髓右侧L4～6背根神经节,检测CBS及NF-κB的表达。结果 CCI组与Sham组比较大鼠术后各时点热痛阈和机械痛阈明显下降(P <0.05),术后7和14 d背根神经节NF-κB p65的表达明显升高(P <0.05);CCI+AOAA组与CCI组比较,术后各时点热痛阈和机械痛阈升高(P <0.05),术后7和14 d背根神经节NF-κB p65表达下调(P <0.05)。结论大鼠神经病理性痛形成与背根神经节CBS的上调,促进NF-κB活化有关。

Objective To evaluate the role of CBS in the development of neuropathic pain in rats. Methods Thirty six SPF healthy male Sprague-Dawley rats,weighing 180 to 200 g,aged 5~6 weeks,in which intrathecal eatheters were successfully implanted,were divided into sham operation group(Sham group),chronic constriction injury group(CCI group)and CBS antagonist AOAA group(CCI+AOAA group),with 12 rats in each group. Intrathecal cathers were successfully implanted after three days,CCI was induced by injury to the sciatic nerve. The sciatic nerve was only exposed but not occluded in Sham group. Intrathecal injection was performed once a day for 14 consecutive days starting from the first day after the operation. Normal saline 20 μL was intrathecally injected in Sham group and CCI group,and AOAA(10 μg/kg)10 μL and normal saline 10 μL were intrathecally injected into CCI + AOAA group. Thermal paw withdrawal threshold (TWT) and mechanical paw withdrawal threshold(MWT)were measured on the day before the operation and 30 min after intrathecal injection on the 1^st, 3^rd,7^th,10^th and 14th day after the operation. The rats were sacrificed and the dorsal root ganglia of the lumbar segment(L4~6)were removed on postoperative 7^th and 14^th day for the determination of the expression of CBS and NF-Bp65. Results Compared with those in Sham group,TWT and MWT were significantly decreased after the operation,and the expression of CBS and NF-κBp65 in dorsal root ganglion were up-regulated on the 7th and 14th day after the operation in CCI group(P < 0.05),Compared with those in CCI group,TWT and MWT were signifi- cantly increased after the operation(P < 0.05). Expression of CBS and NF-κBp65 in dorsal root ganglion were down-regulated on the 7th and 14th day after the operation in CCI + AOAA group(P < 0.05). Conclusion The development of neuropathic pain in rats is associated with the up?regulation of CBS in the dorsal root ganglion and promotion of NF?κB activation.