丙戊茶碱对趾部切口痛大鼠脊髓ERK1/2磷酸化的影响  

EFFECTS OF PROPENTOFYLLINE ON THE PHOSPHORYLATION OF ERK1/2 IN A RAT MODEL OF INCISIONAL PAIN

作　　者：金旭 石翊飒[2] 张东 武琰娇 JIN Xu;SHI Yi-Sa;ZHANG Dong;WU Yan-Jiao(The Second Clinical Medical School, Lanzhou University, Lanzhou, 730000, China;Department of Anesthesiology,The Second Hospital of Lanzhou University, Lanzhou, 730030, China)

机构地区：[1]兰州大学第二临床医学院麻醉医学系,兰州730000 [2]兰州大学第二医院麻醉科,兰州730030

出　　处：《中国疼痛医学杂志》2019年第5期331-337,共7页Chinese Journal of Pain Medicine

摘　　要：目的:研究丙戊茶碱对趾部切口痛模型大鼠脊髓细胞外信号调节激酶1/2 (extracellular signalregulated kinase 1/2, ERK1/2)磷酸化的影响,探讨丙戊茶碱缓解术后急性痛觉过敏的分子机制。方法:雄性SD大鼠100只,随机分为4组(n=25):空白对照组(C组);切口痛模型组(IP组);生理盐水组(NS组);丙戊茶碱组(PPF组)。IP组、NS组和PPF组均制备趾部切口痛(incisional pain, IP)模型。NS组和PPF组分别于术前30 min鞘内注射生理盐水(10μl)和丙戊茶碱(10μg/10μl)。各组分别在术前、术后2、4、8、24、72 h测定机械缩足阈值(mechanical withdrawal threshold, MWT)和热缩足潜伏期(thermal withdrawal latency, TWL)。各组于术前、术后2、4、24、72 h行为学测定后随机留取大鼠L4-6节段脊髓,应用蛋白印迹法检测磷酸化ERK1/2 (phospho-ERK1/2, p-ERK1/2)表达水平。各组于术后p-ERK1/2表达量最高时,取大鼠脊髓应用免疫荧光法检测丙戊茶碱对ERK1/2磷酸化的影响,同时检测p-ERK1/2与脊髓神经元、星型胶质细胞和小胶质细胞标记物的共表达情况。结果:各组术前MWT、TWL及p-ERK1/2表达量差异无统计学意义。与C组比较,IP组术后各时间点MWT和TWL均明显降低(P <0.001),p-ERK1/2表达量在术后2 h (P <0.01)、4 h (P <0.001)、24 h (P <0.005)增加,术后72 h (P <0.01)减少;与IP组比较,NS组术后各时间点MWT、TWL及p-ERK1/2表达量差异无统计学意义;与IP组比较,PPF组术后各时间点MWT和TWL升高(P <0.01),术后2、4、24 h的p-ERK1/2表达量减少(P <0.01),术后72 h表达量差异无统计学意义;与NS组比较,PPF组术后各时间点MWT和TWL均升高(P <0.001),术后2、4、24 h的p-ERK1/2表达量减少(P <0.01),术后72 h表达量差异无统计学意义。免疫荧光结果显示,术后4 h的IP组大鼠脊髓p-ERK1/2在背角浅层的神经元、星型胶质细胞和小胶质细胞内均有表达。结论:丙戊茶碱缓解趾部切口痛模型大鼠术后急性痛觉过敏的作用可能与抑�Objective: To investigate the effect of Propentofylline on the phosphorylation of extracellular signal-regulated kinase 1/2(ERK1/2) in the spinal cord of rats with incisional pain and discuss possible mechanisms of propentofylline relieving acute postoperative hyperalgesia. Methods: One hundred male SD rats were randomly divided into four groups(n = 25 each): the blank control group(C group), the incisional pain model group(IP group), the IP with normal saline group(NS group), the IP with propentofylline group(PPF group). The incisional pain model was prepared in IP group, NS group and PPF group. The NS group and PPF group respectively received intrathecal injection with normal saline(10 μl) and propentofylline(10 μg/10 μl) 30 min before operation. The mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were measured at different time points, including pre-operation and 2, 4,8, 24, 72 h after operation. At the same time, the L4-6 spinal cords were collected immediately. The expression of phospho-ERK1/2(p-ERK1/2) were detected by Western Blot. When the expression of p-ERK1/2 were the highest after operation, their coexpression with different cells in the spinal cord and the influence of propentofylline on phosphorylation of ERK1/2 were detected by immunofluorescence.Results: Before the operation, there was no statistical difference in MWT, TWL and expression of p-ERK1/2 among these groups. Compared with the group C, both MWT and TWL were signi?cantly decreased after operation in group IP and the expression of p-ERK1/2 were increased at 2, 4, 24 h, but decreased at 72 h after operation. Compared with the group IP, there was no statistical difference in MWT, TWL and expression of p-ERK1/2 after operation in group NS. Compared with the group IP, both MWT and TWL were significantly increased in group PPF after operation. However, compared with the group IP, the expression of p-ERK1/2 were significantly reduced at 2, 4, 24 h after operation in group PPF, but no statistical difference at 72 h aft

关 键 词：丙戊茶碱 切口痛 细胞外信号调节激酶 1/2 急性痛 痛觉过敏 

分 类 号：R965[医药卫生—药理学]