国际麻醉学与复苏杂志   2015, Issue (1): 10-10
    
鞘内注射sigma-1受体抑制剂BD1047对神经病理性痛大鼠的镇痛作用及对脊髓小胶质细胞活化的影响
王晨晨, 朱珊珊1()
1.徐州医学院
The effects of intrathecal administration of sigma-1 receptor antagonist BD1047 on the pain behavior and spinal ionized calcium binding adaptor-1 expression of neuropathic pain rats
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摘要:

目的 探讨鞘内注射sigma-1受体抑制剂BD1047对神经病理性痛(neuropathic pain, NP)大鼠痛阈和脊髓小胶质细胞活化的影响。 方法 采用坐骨神经慢性压迫损伤法(chronic constriction injury of sciatic nerve, CCI)建立NP模型。① 雄性Sprague-Dawley(SD)大鼠24只,采用随机数字表法将大鼠分为3组(每组8只):假手术组(S组)、CCI组(C组)和CCI+BD1047组(B组)。术后第0~5天,S组和C组鞘内注射生理盐水(20 μl,1 次/d,连续6 d);B组鞘内注射BD1047(120 nmol/20 μl,1 次/d,连续6 d)。于术前1 d,术后3、5、7、10、14 d,测定大鼠机械缩足反射阈值(paw withdrawal mechanical threshold, PWMT)。② 雄性SD大鼠12只,分组(每组4只)和给药同第1部分实验。术后第10天处死,免疫荧光技术观察脊髓小胶质细胞的染色情况。 结果 与S组比较,C组大鼠术后第3天PWMT[(4.9±0.9) g]开始降低,持续到术后第14天(P<0.05),术后第10天脊髓背角小胶质细胞数[(149±28) 个]明显增加(P<0.05);与C组比较,B组大鼠术后第3天PWMT[(8.6±1.2) g]明显升高,持续到术后第14天(P<0.05),术后第10天脊髓背角小胶质细胞数[(92±22) 个]明显减少(P<0.05)。 结论 鞘内注射BD1047可减轻大鼠NP,其机制与抑制脊髓小胶质细胞活化有关。

关键词: 神经病理性疼痛; sigma-1受体; 小胶质细胞; 脊髓
Abstract:

Objective To explore the effects of intrathecal injection of sigma-1 receptor antagonist BD1047 for neuropathic pain(NP) rats pain threshold and activation of spinal microglia. Methods The left common sciatic nerve of anesthetized rats was tied loosely to establish the chronic constriction injury(CCI) model. ① Twenty-four Sprague-Dawley(SD) male rats were randomized into three groups(n=8): sham group(group S), CCIgroup(group C) and CCI+BD1047 group (group B). Saline(20 μl) or BD1047(120 nmol/20 μl) were given intrathecally once a day for 6 days starting from day 0 after operation. Paw withdrawal mechanical threshold(PWMT) was measured one day before operation and on day 3,5,7,10,14 after operation. ② Twelve SD male rats were randomized into three groups(n=4), the grouping and handling method are the same as Part one. Rats were killed on day 10 after operation and the L4-L6 spinal cord segments were removed to measure the expression of microglial by immunofluorescence techniques. Results Compared with group S, PWMT[(4.9±0.9) g]were significantly decreased since the third day after operation and microglial cells(149±28) were significantly increased on day 10 after operation in group C(P<0.05). Compared with group C, PWMT[(8.6±1.2) g]were significantly increased since the third day after operation and microglial cells (92±22) were significantly decreased on day 10 after operation in group B(P<0.05). Conclusions Intrathecal treatment of BD1047 relieves mechanical allodynia by inhibiting the activation of spinal microglial cells of NP rats.

Key words: Neuropathic pain; Sigma-1 receptor; Microglial; Spinal cord