白屈菜红碱预先给药对神经病理性疼痛大鼠疼痛行为和脊髓星形胶质细胞活化的影响

Effect of chelerythrine pretreatment on pain behavior and spinal astrocytes activation in rats with neuropathic pain

目的 观察蛋白激酶α（PKCα）抑制剂白屈菜红碱（CHE）预先给药对坐骨神经慢性结扎损伤（CCI）大鼠机械疼痛行为和脊髓星形胶质细胞活化的影响.方法 健康雄性SD大鼠128只,250～300 g,采用随机数字表法,随机均分为四组：假手术组（S组）、神经病理性疼痛组（NP组）、生理盐水组（NS组）和CHE组（CH组）.CCI模型建立前给药,CH组用CHE 80 mg/kg灌胃,NS组给予等容量的生理盐水,1次/日,连续4d,NP组不给予任何药物.灌胃结束后S组分离暴露坐骨神经不结扎,余三组制备CCI模型.观察四组大鼠CCI模型建立前（T0）及建立后1 d（T1）、4d（T2）、7 d（T3）、10 d（T4）、14 d（T5）、21 d（T6）、28 d（T7）疼痛行为学改变,并于各时点行为学观察结束时每组随机取4只大鼠,测定脊髓背角胶质纤维酸性蛋白（GFAP）表达和星形胶质细胞计数.结果 与S组比较,T1～T7时NP、NS、CH组机械缩足反应阈值（MWT）明显降低,热缩足反射潜伏期（TWL）明显缩短,脊髓背角GFAP表达及星形胶质细胞计数明显增加（P＜0.05）;与CH组比较,T1～T7时NP组和NS组MWT明显降低,TWL明显缩短（P＜0.05）;T4～T7时脊髓背角GFAP表达及星形胶质细胞计数明显增加（P＜0.05）.结论 白屈菜红碱预先给药可抑制大鼠脊髓星形胶质细胞的活化,从而减轻神经病理性疼痛行为.

Objective To investigate the effect of PKC inhibitor chelerythrine pretreatment on pain behavior and spinal astrocytes activation in rats with neuropathic pain.Methods One hundred and twenty-eight adult male SD rats weighting 250-300 g were randomly divided into four groups （n =32）：sham operation group （group S）,neuropathic pain group （group NP）,normal saline group （group NS） and chelerythrine group （group CH）.Drugs were given before CCI model established,once a day,for four days.Group CH received chelerythrine intragastricly and group NS received intragastric normal saline.Pain behavior was assessed at 1 day before （T0） and 1 d （T1）,4 d（T2）,7 d （T3）,10 d（T4）,14 d （T5）,21 d （T6） and 28 d （T7） after CCI model established.Four rats were sacrificed at each time point in each group for the expression of GFAP in the spinal dorsal horn and the astrocytes was counted.Results Compared with group S,MWT was significantly decreased and TWL was shorted,the expression of GFAP in the spinal dorsal horn was increased,and the astrocytes count was increased at T1-T7 in the other 3 groups（P〈0.05）.Compared with group NP and NS,MWT was significantly increased,TWL was prolonged at T1-T7 （P〈0.05）,the expression of GFAP in the spinal dorsal horn was decreased,and the astrocytes count was decreased at T4-T7 in group CH （P 〈0.05）.Conclusion Chelerythrine pretreatment can inhibits spinal astrocytes activation and reduce neuropathic pain behavior.