川芎嗪对神经病理性痛大鼠背根神经节GAP-43 mRNA表达的影响

Effect of tetramethylpyzine on expression of GAP-43 mRNA in dorsal root ganglion in a rat model of neuropathic pain

目的 评价川芎嗪对神经病理性痛大鼠背根神经节生长相关蛋白-43（GAP-43） mRNA表达的影响.方法 健康成年雄性Wistar大鼠54只,体重180～220 g,6～8周龄,采用随机数字表法分为3组（n=18）：假手术组（S组）、神经病理性痛组（NP组）和川芎嗪组（TMP组）.NP组和TMP组采用坐骨神经慢性压迫损伤法建立神经病理性痛模型,S组仅暴露坐骨神经不结扎.TMP组于术毕即刻开始腹腔注射川芎嗪100 mg·kg-1 ·d-1,连续14 d;S组和NP组腹腔注射等容量生理盐水.于术前1d、术后3、7、14 d（T0-3）时随机取6只大鼠,测定机械痛阈（MWT）和热痛阈（TWL）,并于T1-3时测定痛阈后处死,取损伤侧L4-6背根神经节,采用实时荧光PCR法检测GAP-43 mRNA的表达水平.结果 与S组比较,NP组和TMP组MWT和TWL降低,背根神经节GAP-43 mRNA表达上调（P＜0.05）.与NP组比较,TMP组MWT和TWL升高,背根神经节GAP-43 mRNA表达下调（P＜0.05）.结论 川芎嗪减轻大鼠神经病理性痛的机制可能与其抑制背根神经节GAP-43 mRNA表达上调有关.

Objective To evaluate the effect of tetramethylpyzine on the expression of growth associated protein-43 （GAP-43） mRNA in the dorsal root ganglion in a rat model of neuropathic pain （NP）.Methods Fiftyfour male Wistar rats,weighing 180-220 g,aged 6-8 weeks,were randomly assigned into 3 groups （n =18 each） using a random number table：sham operation group （group S）,NP group and tetramethylpyzine group （group TMP）.NP was induced by chronic constrictive injury in anesthetized rats in NP and TMP groups.The sciatic nerve was exposed and 4 loose ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread.In group S,the right sciatic nerve was only exposed but not ligated.In group TMP,tetramethypylrazine 100 mg· kg-1 · d-1 was injected intraperitoneally for 14 consecutive days starting from the end of operation,while the equal volume of normal saline was administered instead of tetramethylpyrazine in S and NP groups.Mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were measured at 1 day before operation （T0,baseline） and 3,7 and 14 days after operation （T1-3）.The animals were then sacrificed after measurement of pain threshold at T1-3.The L4-6 segments of dorsal root ganglions on the injured side were removed for determination of the expression of GAP-43 mRNA using real-time fluorescent PCR.Results Compared with group S,MWT and TWL were significantly decreased,and the expression of GAP-43 mRNA was up-regulated in NP and TMP groups （P 〈 0.05）.Compared with group NP,MWT and TML were significantly increased,and the expression of GAP43 mRNA was down-regulated in group TMP （P 〈 0.05）.Conclusion The mechanism by which tetramethylpyrazine attenuates NP may be related to inhibition of the expression of GAP-43 mRNA in the dorsal root ganglion of rats.