鞘内注射GDNF对神经病理性痛大鼠脊髓背角p38MAPK蛋白表达的影响

目的 评价鞘内注射胶质细胞源性神经营养因子(GDNF)对神经病理性痛大鼠脊髓背角p38丝裂原活化蛋白激酶(p38MAPK)蛋白表达的影响.方法 取鞘内置管成功的健康雄性SD大鼠120只,周龄6周,体重180～200 g,随机分为4组(n=30):对照组(C组)、假手术组(S组)、神经病理性痛组(P组)和GDNF组.采用结扎L5.6脊神经的方法建立大鼠神经病理性痛模型.C组不给予任何处理;S组只暴露脊神经,但不结扎;P组脊神经结扎后鞘内注射生理盐水10μl,隔日1次,连续14 d;GDNF组脊神经结扎后鞘内注射GDNF 2μg,用生理盐水稀释至10μl,隔日1次,连续14 d.分别于脊神经结扎后3、7和14 d时,取10只大鼠,测定机械痛阈,然后处死,取脊髓背角,分别采用免疫组化法和蛋白质印迹法测定p38MAPK蛋白的表达水平.结果 与S组比较,P组和GDNF组机械痛阈降低,脊髓背角p38MAPK蛋白表达上调(P＜0.05或0.01);与P组比较,GDNF组机械痛阈升高,脊髓背角p38MAPK蛋白表达下调(P＜0.05或0.01).结论 鞘内注射GDNF可通过抑制脊髓背角p38MAPK蛋白的表达减轻大鼠神经病理性痛.

Effect of intrathecal glial cell line-derived neurotrophic factor on p38MAPK protein expression in spinal dorsal horn in a rat model of neuropathic pain

Objective To investigate the effect of intrathecal glial cell line-derived neurotrophic factor (GDNF) on p38 mitogen-activated protein kinase (p38MAPK) protein expression in the spinal cord dorsal horn in a rat model of neuropathic pain. Methods Male SD rats 6 weeks old weighing 180-200 g were used in this study.One hundred and twenty rats in which intrathecal catheters was successfully implanted were randomly divided into 4 groups ( n = 30 each): group Ⅰ control ( group C); group Ⅱ sham operation ( group S); group Ⅲ neuropathicpain (group P) and group Ⅳ GDNF. In groupⅢ and Ⅳ I6 spinal nerve was ligated. In group Ⅳ intrathecal GDNF was administered every other day for 14 d after spinal nerve ligation. In group Ⅲ normal saline was given instead. Ten animals from each group were selected at 3, 7 and 14 d after spinal nerve ligation, the mechanical pain threshold was measured, and then the rats were decapitated. The I4-6 segment of the spinal cord of the operated side was isolated. p38MAPK protein expression in the spinul dorsal horn was determined by immunohistochemistry and Western blotting. Results Intrathecal GDNF significantly attenuated spinal nerve ligationinduced increase in p38MAPK protein expression in spinal dorsal horn of the operated side. Conclusion IT GDNF can relieve neuropathic pain by inhibiting p38MAPK protein expression in the spinal dorsal horn.