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阿米替林抑制神经性疼痛大鼠脊髓星形胶质细胞的激活 被引量:7

Amitriptyline inhibits activation of astrocytes in spinal cord of rat with neuropathic pain
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摘要 目的观察阿米替林对分支选择结扎模型(spared nerve injury,SNI)大鼠脊髓星形胶质细胞激活程度的影响。方法120只雄性SD大鼠,分为对照组(A)、SNI模型组(B)、单纯给药组(C)、SNI模型+药物干预组(D),经腹腔分别给予0.2ml生理盐水(A、B)、10mg/kg阿米替林(C、D),每日2次。术后1、3、5d取L3~L6脊髓,分别进行星形胶质细胞激活标志物GFAP免疫荧光染色、Western blot和半定量RT—PCR检测,同时观察机械痛阈值改变。结果与A组相比,B组大鼠机械痛阈值随时间下降明显(P〈0.05),GFAP蛋白表达(0.38±0.24,0.84±0.31,1.36±0.43)和mRNA表达(0.55±0.14,0.86±0.16,1.32±0.32)随时间逐渐增强;C组各项指标与A组比较无明显差异;D组大鼠给药后3、5d机械痛阈值停止下降[(4.5±1.5)、(4.9±1.4)g],GFAP蛋白(0.79±0.25,0.77±0.23)和mRNA(0.63±0.06,0.64±0.17)表达较A组略增高,但不及B组(P〈0.05)。结论阿米替林可能通过抑制星形胶质细胞激活,发挥治疗神经病理性疼痛作用。 Objective To investigate influence of amitriptyline on astrocytic activation in spinal cord of rats after spared nerve injury (SNI). Methods A total of 120 male SD rats were randomly divided into 4 groups with 30 rats in each group : control ( A), SNI ( B), amitriptyline ( C), and SNI + amitriptyline (D) groups, which respectively were treated with intraperitoneal injections of 0. 2 ml normal saline (A and B) , 10 mg/kg amitriptyline ( C and D), bid. The L3 to L6 segment of the spinal cord was isolated respectively at 1, 3 and 5 d after surgery. Expression of glial fibrillary acidic protein (GFAP), marker of astrocytes, was determined by immunofluorescence, Western blot assay and semiquantitative RT-PCR. The changes of mechanical pain threshold were measured. Results Compared with control, group B had a markedly decreased rat mechanical pain threshold ( P 〈 0. 05) and an obviously high expression of GFAP at both protein (0.38 ±0.24, 0.84 ±0.31 and 1.36 ±0.43) and mRNA (0.55 ±0.14, 0. 86±0.16, 1.32 ±0.32) levels at the corresponding time points. However, there was no significant change on these indexes between groups A and C. Mechanical pain threshold of rats in group D did not change any more in 3 and 5 d after surgery (4.5 ± 1.5 and 4.9 ± 1.4 g). In addition, the expression of GFAP at both protein (0.79 ± 0.25, O. 77± 0.23) and mRNA (0.63 ±0. 06, 0. 64 ±0.17) levels in group D were higher than those in control but still lower than those of group B (P 〈 0. 05 ) in 3 and 5 d after surgery. Conclusion Amitriptyline inhibits the activation of astrocytes in SNI animals, which maybe one of its mechanisms in the treatment of neuropathic pain.
出处 《第三军医大学学报》 CAS CSCD 北大核心 2009年第7期611-614,共4页 Journal of Third Military Medical University
关键词 神经性疼痛 星形胶质细胞 抗抑郁药 GFAP neuropathic pain astrocyte antidepressant glial fibrillary acidic protein
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