目的 :观察神经病理性疼痛模型大鼠脊髓组织中(sonic hedgehog,Shh)信号通路的表达及随时间的动态变化规律,探索其在神经病理性疼痛中所发挥的作用。方法:取80只成年SD大鼠,采用随机数字表法均分为假手术组(sham operation group,Sham)与坐骨神经慢性压迫模型(chronic constriction injury of the sciatic nerve,CCI)组。CCI组(n=40)左侧坐骨神经以4.0丝线结扎,Sham组(n=40)不结扎,仅暴露左侧坐骨神经。建模后1、4、7、14、28 d分别对2组大鼠进行一般行为学观察,并测定大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT);采用Western blot和免疫组化检测大鼠脊髓腰骶膨大部(L4~6节段)的Shh、Gli表达。结果:与Sham组相同时间点比较:CCI组术前MWT(P=0.832)差异无统计学意义,术后其余各时间点均明显降低(P<0.01)具有统计学意义;CCI组内不同时间点比较:术后第1天MWT开始明显降低(P=0.002),7 d达到最低值(P=0.027),28 d仍处于较低的水平(P=0.003)。Western blot结果显示:与Sham组相同时间点比较:CCI组术后1 d大鼠脊髓腰骶膨大部Shh、Gli蛋白表达没有明显变化(P=0.215),其余各时间点Shh、Gli蛋白表达均出现明显增加(P<0.01);CCI组内不同时间点比较:术后7 d Shh、Gli蛋白表达水平达到最大值(P<0.01),这种高水平的表达可持续到损伤后28 d(P<0.01)。免疫组化结果显示:与Sham组比较:CCI术后第7天Shh、Gli蛋白在相应区域显示染色明显增加(P<0.01)。结论:神经病理性疼痛的发生、发展与Shh通路的激活具有显著相关,其通路蛋白的表达第7天达到峰值,第28天仍处于较高水平。 OBJECTIVE: To observe the expression of sonic hedgehog (Shh) signaling pathway in rat model of neuropathic pain and its dynamic change with time, and to explore its role in neuropathic pain. Methods: Eighty adult SD rats were randomly divided into sham operation group (Sham) and chronic constriction injury of the sciatic nerve (CCI) group. The left sciatic nerve in the CCI group (n = 40) was ligated with 4.0 silk thread, while the Sham group (n = 40) was not ligated, exposing only the left sciatic nerve. At 1, 4, 7, 14 and 28 days after modeling, the general behavioral observation was performed on the two groups of rats and the mechanical withdrawal threshold (MWT) was measured. Western blot and immunohistochemistry Expression of Shh and Gli in lumbosacral region (L4 ~ 6 segments) in rat spinal cord. Results: Compared with Sham group at the same time point, there was no significant difference in preoperative MWT (P = 0.832) between CCI group and postoperative CCI group at different time points (P <0.01) MWT was significantly lower on the first postoperative day (P = 0.002), reached the lowest value on the seventh day (P = 0.027), and remained relatively low on the 28th day (P = 0.003). Western blot results showed that Shh and Gli protein expression in the lumbosacral region of the spinal cord did not change significantly (P = 0.215) at 1 d after operation in CCI group compared with Sham group at the same time point (P <0.01). At different time points in CCI group, Shh and Gli protein expression reached the maximum (P <0.01) on the 7th day after operation, and this high level expression continued to the 28th day after injury P <0.01). The results of immunohistochemistry showed that compared with Sham group, the expression of Shh and Gli protein in the corresponding area showed a significant increase (P <0.01) on the 7th day after CCI. CONCLUSIONS: The occurrence and development of neuropathic pain are significantly correlated with the activation of Shh pathway. The expression of its pathway protein peaked on the 7th day and remained high at 28 days.