国际麻醉学与复苏杂志   2011, Issue (2): 0-0
    
己酮可可碱对术后痛模型大鼠脊髓胶质细胞激活的影响
刘志龙1()
1.兰州大学第二医院麻醉科
Effect of Pentoxiflline on the spinal cord glial activation in a rat model of postoperative pain
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摘要:

【摘要】 目的 观察腹腔注射己酮可可碱对术后痛模型大鼠的抗痛觉过敏及对脊髓胶质细胞激活的影响作用。方法 健康雄性SD大鼠60只,体重190~220g,采用数字表法随机随机分为2组(n=30):对照组(NS组),实验组(PTX组)。本研究选择趾部切口术后痛大鼠模型。PTX组从术前15分钟起至术后5天,每日一次腹腔注射己酮可可碱50mg/kg,生理盐水治疗组在相同时间点给予等容量生理盐水。分别于术前1天和术后1h、2h、3h、5h、1d、2d、3d、5d天腹腔注射药物后30~55分钟后,随机取6只大鼠,进行累计疼痛评分(cumulative pain score)和机械缩足反射时间(Paw withdrawal threshold ,PWT)的测定,并于术后1、2、3、5天测定结束后处死,免疫组化观察脊髓星形胶质细胞标记物胶质纤维酸性蛋白(glial fibrillary acid protein,GFAP)和小胶质细胞标记物离子钙接头蛋白抗体(Ionized calcium bindingadaptor molecule-1,Iba-1)的表达。结果 ①术后1h、2h、3h、5h、1d、2d、3d累计疼痛评分,PTX组分别为2.98±0.43、3.96±0.84、6.65±0.57、8.68±0.74、10.28±0.48、7.05±0.68、5.65±0.54,和NS组4.06±0.67、6.09±0.18、8.82±0.24、11.08±0.56、13.12±0.23、9.56±0.78、7.82±0.67相比下降(P<0.05);②术后1h、2h、3h、5h、1d、2d、3dPWT,PTX组分别为5.84±1.60、5.25±1.17、4.47±0.67、4.90±0.48、5.25±1.17、7.60±1.85、10.49±1.62,和NS组2.48±0.87、2.14±0.56、2.08±0.53、2.19±0.38、2.37±0.56、4.54±0.96、8.13±1.49相比增加 (P<0.05);③术后1d、2d、3d脊髓背角GFAP表达,PTX组分别为181.21±4.18、205.67±4.26、230.24±3.24和NS组244.12±4.92、258.60±4.12、276.27±3.48相比表达下调(P<0.05)。④术后3d、5d脊髓背角Iba-1表达,PTX组分别为168.24±3.24、170.66±3.99和NS组230.27±3.48、205.28±4.05相比表达下调(P<0.05)。结论 腹腔注射己酮可可碱减轻术后痛模型大鼠的痛觉过敏机制可能与抑制脊髓胶质细胞的激活有关。

关键词: 己酮可可碱;术后痛;星形胶质细胞;小胶质细胞
Abstract:

【Abstract】 Objective To investigate the effect of intraperitoneally administration of pentoxifylline on the development of hyperalgesia and the activation of glial cells in a rat model of postoperative pain . Methods Sixty male SD rats weight 190~220g were randomly divided into 2 groups: control group (NS group) and treatment group(PTX group), in which 50mg/kg saline vehicle or pentoxifylline treatment (n=30) was given by the intraperitoneally route 15min before surgery and continued daily to day 5 operation, respectively.The animal model of postoperative pain was established by incisioning hind paw. cumulative pain score and paw withdrawal threshold were measured at 1 day before operation and then at 1, 2, 3, and 5 hours and 1, 2, 3, and 5 days after operation. Spinal cord tissue samples from rats were taken for analysis of glial fibrillary acid protein(GFAP) and ionized calcium bindingadaptor molecule-1(Iba-1) expression by means of immunohistochemistry at the following times after operation: 1, 2, 3, and 5 days. Results ①At the following times after surgery: 1,2,3,5 hours and1,2d,3 days, the cumulative pain score were 2.98±0.43,3.96±0.84,6.65±0.57,8.68±0.74,10.28±0.48,7.05±0.68 and 5.65±0.54 in the PTX group respectively, less than the NS group with 4.06±0.67,6.09±0.18, 8.82±0.24, 11.08±0.56,13.12±0.23,9.56±0.78 and 7.82±0.67(P<0.05).② At the following times after surgery: 1,2,3,5 hours and 1,2 and 3 days,the PWT were 5.84±1.60,5.25±1.17,4.47±0.6,4.90±0.48,5.25±1.1,7.60±1.8 and 10.49±1.6 in the PTX group respectively, more than the NS group with 2.48±0.87,2.14±0.56,2.08±0.5,2.19±0.3,2.37±0.56,4.54±0.96 and 8.13±1.49(P<0.05).③The GFAP expression in the spinal cord tissue at the following times after surgery: 1,2 days and 3 days were 181.21±4.18,205.67±4.26 and 230.24±3.24 in the PTX group respectively, lower than the NS group with 244.12±4.9,258.60±4.12 and 276.27±3.48(P<0.05).④The Iba-1 expression in the spinal cord tissue at the following times after surgery: 3 days and 5 days were 168.24±3.24 and 170.66±3.99 in the PTX group respectively, lower than the NS group with 230.27±3.48 and 205.28±4.05(P<0.05).Conclusion pentoxifylline can attenuate the process of mechanical allodynia in a rat model of postoperative pain, the main mechanism may be inhibiting glial cells activation in the spinal cord.

Key words: Pentoxifylline; Postoperative pain ; Astrocyte;Microglia