目的 探讨磷酸化c-Jun氨基末端激酶（phosphorylated c-Jun N-terminal kinase, p-JNK）在银杏叶提取物（Ginkgo biloba extract, EGb761）缓解神经病理性疼痛中的作用。 方法 采用随机数字表法将90只雄性SD大鼠分成5组（每组18只）：假手术组（Sham组）、坐骨神经慢性压迫损伤（chronic constriction injury, CCI）组（CCI组）、EGb761 50 mg/kg+CCI组（EGb50组）、EGb761 100 mg/kg+CCI组（EGb100组）、溶剂对照+CCI组（SC组）。CCI组大鼠分离并结扎左侧坐骨神经，Sham组大鼠只分离神经不结扎；其余各组于造模成功后第3天开始腹腔注射EGb761或者溶剂，持续到术后14 d。分别于术前2 d和术后1、3、5、7、10、14 d测定机械刺激缩足反射阈值（paw mechanical withdrawal threshold, PMWT）和热刺激缩足反射潜伏期（paw withdraw thermal latency, PWTL），于术后14 d取同侧背根神经节，采用免疫组织化学和Western blot法检测背根神经节中p-JNK阳性细胞率及表达水平。 结果 与Sham组比较，CCI组和SC组术后各时间点PMWT和PTWL明显降低（P<0.05），术后14 d背根神经节p-JNK阳性细胞率及表达水平明显升高（P<0.05）。与CCI组比较，EGb50组和EGb100组术后7、10、14 d PMWT和PTWL明显提高（P<0.05），术后14 d背根神经节p-JNK阳性细胞率和表达水平明显降低（P<0.05）。与EGb50组比较，EGb100组术后10、14 d PMWT、PTWL明显升高（P<0.05），术后14 d背根神经节p-JNK阳性细胞率和表达水平明显降低（P<0.05）。 结论 EGb761可通过抑制背根神经节p-JNK的表达而缓解CCI大鼠神经病理性疼痛。
Objective To investigate the role of phosphorylated c-Jun N-terminal kinase (p-JNK) in Ginkgo biloba extract (EGb761) to alleviate neuropathic pain. Methods A total of 90 male SD rats were randomly divided into 5 groups (n=18): a sham operation group (group Sham), chronic constriction injury group (group CCI), EGb 50 mg/kg+CCI group (group EGb50), EGb 100 mg/kg+CCI group (group EGb100) and a solvent control+CCI group (group SC). Rats in group CCI were subjected to ligation of the left sciatic nerve, while those in group Sham underwent nerve separation without ligation. Other groups were intraperitoneally injected with EGb761 or solvent from day 3 after successful modeling to 14 d after surgery. Paw withdraw thermal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured 2 d before and 1, 3, 5, 7, 10 d and 14 d after surgery. Then, the ipsilateral dorsal root ganglion were collected on 14 d after surgery. The levels of p-JNK in the dorsal root ganglion and spinal dorsal horn were determined by immunochemistry and Western blot. Results Compared with group Sham, groups CCI and SC showed remarkable decreases in PMWT and PTWL at each time points (P<0.05), and marked increases in the positive rate and levels of p-JNK in the dorsal root ganglion 14 d after surgery (P<0.05). Compared with group CCI, groups EGb50 and EGb100 showed remarkable increases in PMWT and PTWL 7, 10 d and 14 d after surgery (P<0.05), and marked decreases in the positive rate and levels of p-JNK (P<0.05). Compared with group EGb50, group EGb100 showed remarkable increases in PMWT and PTWL 10 d and 14 d after surgery (P<0.05), and presented substantial decreases in the positive rate and levels of p-JNK in the dorsal root ganglion 14 d after surgery (P<0.05). Conclusions EGb761 may ameliorate neuropathic pain of rats with CCI through inhibiting the expression of p-JNK in the dorsal root ganglia.
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