加波沙朵对神经病理性痛大鼠的镇痛作用及对脊髓胶质细胞活化的影响

目的 探讨皮下注射γ-氨基丁酸(γ aminobutyric acid,GABA)A型受体激动剂加波沙朵对神经病理性痛(neuropathic pain,NP)大鼠痛阈和脊髓星形胶质细胞活化的影响. 方法 用坐骨神经慢性压迫损伤(chronic constriction injury of sciatic nerve,CCI)法建立NP模型.雄性SD大鼠36只,采用随机数字表法分为3组(每组12只):假手术组(S组)、CCI组(C组)和CCI+加沙波朵组(G组).术后10～14 d,S组和C组分别皮下注射生理盐水,G组皮下注射加波沙朵10 mg/kg,1次/d.每组随机选取8只大鼠,分别于术前,术后3d,术后10 d给药前,术后14 d给药后0.5、1、2、4、8、12 h,测定大鼠机械缩足反射阈值(paw withdrawal mechanical threshold,PWMT).每组取4只大鼠,于术后14 d给药后2h处死,采用免疫荧光技术观察脊髓星形胶质细胞的染色情况. 结果 与S组比较,C组大鼠术后3 d PWMT[(13.46±1.67)g比(4.65±0.46)g]开始降低,持续到术后14 d给药后12 h(P＜0.05),术后14d给药后2h脊髓背角星形胶质细胞数明显增加[(103±7)个比(402 ±20)个](P＜0.05);与C组比较,G组大鼠术后14 d给药后0.5 h PWMT[(2.73±0.57)g比(7.31±0.55)g]明显升高,持续到给药后8 h(P＜0.05),术后14 d给药后2h脊髓背角星形胶质细胞数明显减少[(251±20)个](P＜0.05). 结论 皮下注射GABAA受体激动剂加波沙朵可减轻大鼠NP,其机制与抑制脊髓星形胶质细胞活化有关.

Effects of gaboxadol on the pain and spinal astrocyte activation of rats with neuropathological pain

Objective To explore the effects of subcutaneous injection of γaminobutyric acid (GABA) A receptor agonist gaboxadol for the pain threshold of rats with neuropathological pain (NP) and the activation of spinal astrocytes.Methods A NP model was established in rats through chronic constriction injury (CCI) of the sciatic nerve.Thirty-six male SD rats were randomized into three groups(n=12):a sham group (group S),a CCI group (group C) and a CCI+gaboxadol group (group G).Then,normal saline or 10 mg/kg gaboxadol was subcutaneously injected in group S,group C or group G respectively,once a day,from Days 10 to 14 after operation.8 rats were randomly selected in each group,and paw withdrawal mechanical threshold (PWMT) was measured one day before operation and on day 3 and 10 after operation,and 0.5,1,2,4,8,12 h after final injection.4 rats were selected in each group,and they were killed sacrificed 2 h after final injection and the expression of astrocytes in the spinal cord was measured by immunofluorescence.Results Compared with group S,rats in group C started to show decreases in PWMT on day 3 after operation [(13.46±1.67) g vs (4.65±0.46) g],which was maintained until 12 h after injection (P＜0.05).Compared with group S,the number of astrocyte cells in group C [(103±7) vs (402±20)] were significantly increased 2 h after injection (P＜0.05).Compared with group C,group G showed remarkable increases in PWMT [(2.73±0.57) g vs (7.31±0.55) g] 0.5 h after injection,which was maintained until 8 h after injection (P＜0.05).Compared with group C,the number of astrocyte cells in group G (251±20) were significantly decreased 2 h after injection (P＜0.05).Conclusions Subcutaneous injection of gaboxadol relieves the mechanical pain in rats,which may be associated with inhibited activation of astrocytes in the spinal cord.