鞘内注射GDNF对神经病理性疼痛大鼠脊髓水平p-Shc表达的影响  

EFFECTS OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR ON THE EXPRESSION OF p-Shc IN SPINAL CORD IN A RAT MODEL OF NEUROPATHIC PAIN

作　　者：高园园[1] 王红军[1] 

机构地区：[1]徐州医科大学江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室,徐州221004

出　　处：《中国疼痛医学杂志》2016年第5期331-336,共6页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(30901402,30900417);江苏省高校自然科学基金(09KJD320008,08KJB180011)

摘　　要：目的：探讨神经病理性疼痛大鼠脊髓背角水平p-Shc的表达变化及鞘内注射胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor,GDNF）对其表达的影响。方法：实验1：雄性SD大鼠随机分为假手术（sham）组和CCI组。CCI组又分为术后1 d组（D1组）、3 d组（D3组）、7 d组（D7组）和14 d组（D14组）,分别于术后1、3、7、14 d测定热缩足潜伏期（thermal withdraw latency,TWL）和机械缩足阈值（mechanical withdrawal threshold,MWT）后处死并取其脊髓背角,采用Western blot方法测定Shc/p-Shc蛋白表达情况。实验2：雄性SD大鼠分为sham组、D14组、D14＋PBS组、D14＋GDNF组。与实验1相同的时间点测定TWL和MWT,并于第14 d处死并取其L4~5脊髓背角,采用Western blot方法检测Shc/p-Shc的表达变化。结果：与sham组相比,CCI组大鼠TWL和MWT明显降低（P〈0.01）;与D14组和D14＋PBS组相比,D14＋GDNF组大鼠TWL和MWT明显升高（P〈0.01）。CCI组脊髓背角内p-Shc表达水平于术后3 d开始升高（P〈0.05）,一直持续到术后14 d（P〈0.01）;D14＋GDNF组p-Shc表达水平较D14组和D14＋PBS组显著下降（P〈0.05）。结论：大鼠脊髓背角内接头蛋白Shc可能参与了神经病理性疼痛的发生,鞘内注射GDNF减轻神经病理性疼痛可能与降低脊髓背角Shc的磷酸化水平有关。Objective：To investigate the effects of intrathecal injection of glial cell line-derived neurotrophic factor（GDNF） on the expression of p-Shc in the spinal cord dorsal horn in a rat model of neuropathic pain. Methods： Experiment 1： Male Sprague-Dawley rats were randomized divided into sham group and CCI group. The CCI group was further divided into 1 d postoperative group（group D1）, 3 d postoperative group（group D3）, 7 d postoperative group（group D7） and 14 d postoperative group（group D14）. Thermal withdrawal latency（TWL） and mechanical withdrawal threshold（MWT） were measured at 1 d, 3 d, 7 d and 14 d after CCI. After determination of TWL and MWT, rats were sacrificed, and the L4-L5 spinal dorsal horn was collected for Western blot. Experiment 2： Male Sprague-Dawley rats were divided into sham group, group D14, D14 combined with treatment of PBS group（D14 ＋ PBS group） and D14 combined with treatment of GDNF group（D14 ＋ GDNF group）.TWL and MWT were measured at the same time point as experiment 1 and the rats were sacrificed at 14 d, then the dorsal horn of the L4-L5 spinal cord was collected for Western blot. Results： Compared with sham group, TWL and MWT of CCI group decreased significantly（P〈0.01）; Compared with group D14 and group D14 ＋ PBS, TWL and MWT of group D14 ＋ GDNF was significantly increased（P〈0.01）.The expression level of p-Shc in CCI group began to increase at 3 d（P〈0.05） and sustained at a high level until 14 days after operation（P〈0.01）; the p-Shc level of D14 ＋ GDNF group decreased significantly compared to that of D14 group and D14 ＋ PBS group（P〈0.05）. Conclusion： The adaptor Shc in the spinal cord dorsal horn may be involved in the development of neuropathic pain, and the alleviation of neuropathic pain by intrathecal administration GDNF is associated with a decrease of p-Shc level in spinal cord dorsal horn.

关 键 词：胶质细胞源性神经营养因子 神经病理性疼痛 磷酸化Shc 

分 类 号：R614[医药卫生—麻醉学]