中文摘要：

目的：观察Janus激酶2（Janus kinase 2， JAK2）/信号转导和转录激活子3（signal transducers and activators of transcription 3， STAT3）通路抑制剂WP1066对神经病理性疼痛的影响。方法12只体重180～200 g雌性SD大鼠用随机数字表法分为WP1066组及对照组（n＝6），均行双侧坐骨神经结扎手术，两组于术前1 d、术前及术后第3、5天分别经鞘内注射容量为10μl的WP1066（10 mmol/L溶于二甲基亚砜）或二甲基亚砜，于术前及术后第3、5、7、10、14天进行动物行为学检测，观察大鼠对机械、热及丙酮冷刺激的反应。术后第14天处死大鼠，于L4～L6腰膨大脊髓背角处取材，使用RT-PCR及Western blot检测STAT3、细胞因子信号抑制因子3（ suppressor of cytokine signaling 3， SOCS3）、 JAK2 mRNA及蛋白水平。结果大鼠机械缩足反射阈值、热刺激缩足反射潜伏期和冷痛阈值分别从第3、5、5天开始， WP1066组较对照组明显升高，差异具有统计学意义（P＜0.05）。与对照组相比， WP1066组STAT3、 SOCS3、 JAK2 mRNA表达均明显降低（ P＜0.05）； WP1066组磷酸化STAT3、 SOCS3、 JAK2蛋白水平均亦明显降低（ P＜0.05）。结论 WP1066可明显改善大鼠神经病理性疼痛，可能为治疗神经病理性疼痛提供新的靶点。

英文摘要：

Objective To evaluate whether the Janus kinase 2 （JAK2）/signal transducers and activators of transcription 3 （ STAT3） inhibitor WP1066 could be a novel therapeutic target for neuropathic pain and its molecu-lar mechnism.Methods Twelve female SD rats weighing 180-200 g were randomly divided into WP1066 group and control group （ n=6） using the random number table .Rats in both groups underwent bilateral chronic sciatic nerve constriction injury （bCCI）.WP1066 （10μl, 10 mmol/L in dimethyl sulfoxide） or the equal volume of dime-thyl sulfoxide was applied through the intrathecal tube one day before surgery , just before surgery , and 3 and 5 days after surgery in the WP1066 group and control group , respectively .Behavior tests were performed before surgery and 3, 5, 7, 10, and 14 days after the surgery to observe the rats＆#39;reactions to mechanical , thermal, and cold stimula-tions.The rats were killed on the 14th postoperative day.The dorsal horn of the spinal cord （L4-L6） was harves-ted, followed by the reverse transcription polymerase chain reaction （ RT-PCR） and Western blotting to investigate the activation of the JAK2/STAT3 pathway.Results The pain-related behavior changes were significantly better in the WP1066 group than in the control group .WP1066 significantly inhibited the JAK2, suppressor of cytokine sig-naling 3 （SOCS3）, and STAT3 mRNA in rats with bCCI, and significantly decreased the ratio of JAK2, SOCS3 and phosphorylation of STAT3 （p-STAT3） protein expression on the 14th postoperative day.Conclusions The administration of WP1066 can remarkably improve neuropathic pain in bCCI rats by inhibiting the STAT 3 signaling pathway.Therefore, WP1066 may be a novel target for neuropathic pain .