国际麻醉学与复苏杂志   2018, Issue (8): 1-1
    
脊髓G蛋白耦联受体激酶2在大鼠持续性术后痛中的作用
胡兴国, 祁乐, 刘功俭, 曾因明1()
1.湖南省桃源县人民医院
Role of spinal G protein-coupled receptor kinase 2 in persistent postoperative pain in rats
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摘要:

目的 研究脊髓G蛋白耦联受体激酶2(G protein-coupled receptor kinase 2, GRK2)在大鼠持续性术后痛中的作用。 方法 鞘内置管成功的雄性SD大鼠60只,采用随机数字表法分为6组(每组10只):假手术组(Ⅰ组)、假手术+溶媒二甲基亚砜(dimethyl sulfoxide, DMSO)组(Ⅱ组)、假手术+GRK2降解抑制剂MDL28170组(Ⅲ组)、皮肤/肌肉切口和牵拉(skin/muscle incision and retraction, SMIR)组(Ⅳ组)、SMIR+DMSO组(Ⅴ组)、SMIR+MDL28170组(Ⅵ组)。应用Yaksh法鞘内置管;采用Flatters法制备大鼠SMIR模型;各组大鼠分别于术前1 d(T0)、术后3 d(T1)、术后7 d(T2)、术后14 d(T3)、术后21 d(T4)用von Frey细丝法测定机械刺激缩足阈值(paw withdrawal mechanical threshold, PWMT);于T3时刻行为学测定后各组随机抽取4只大鼠处死,取L4~L6节段脊髓组织,采用Western blot法检测脊髓GRK2的表达。 结果 与Ⅰ组比较,Ⅳ组和Ⅴ组T1~T4时PWMT明显降低(P<0.05),Ⅵ组T1~T3时PWMT明显降低(P<0.05);T1~T4时,与Ⅳ组比较,Ⅵ组PWMT明显升高(P<0.05)。与Ⅰ组比较,Ⅳ组和Ⅴ组大鼠脊髓GRK2表达明显下调(P<0.05);与Ⅳ组比较,Ⅵ组大鼠脊髓GRK2表达明显上调(P<0.05)。 结论 脊髓GRK2表达水平下调与大鼠SMIR持续性术后痛的发生、发展有关。

关键词: G蛋白耦联受体激酶2; 疼痛,手术后; 痛觉过敏; 脊髓
Abstract:

Objective To investigate the role of spinal G protein-coupled receptor kinases 2(GRK2) in persistent postoperative pain after skin/muscle incision and retraction (SMIR) in rats. Methods Sixty male SD rats in which intrathecal catheter were successfully implanted were divided randomly into 6 groups (n=10): sham operation group (group Ⅰ), sham + dimethyl sulfoxide (DMSO) group (group Ⅱ), sham+MDL28170 group (group Ⅲ), SMIR group (group Ⅳ), SMIR+DMSO group (group Ⅴ), SMIR+MDL28170 group (group Ⅵ). A PE-10 catheter was inserted into the subarachnoid space (intrathecal). A rat model of persistent post-operative pain was established with SMIR. Pain behavior was assessed with von Frey filament test and was quantified with paw withdrawal mechanical threshold (PWMT) 1 d before operation (T0) and 3 d (T1), 7 d (T2), 14 d (T3) and 21 d (T4) after operation. Four rats in each group were sacrificed at T3, the L4-L6 segments of the spinal cord were obtained to determine the protein levels of GRK2 with Western blot assay. Results Compared with groupⅠ, the PWMT was significantly decreased at T1-T4 in group Ⅳ and group Ⅴ(P<0.05), and at T1-T3 in group Ⅵ(P<0.05). Compared with group Ⅰ, the protein levels of spinal GRK2 was down-regulated at T3 in group Ⅳ and group Ⅴ(P<0.05). Compared with group Ⅳ, the spinal GRK2 was upregulated at T3 in group Ⅵ(P<0.05). Conclusions The down-regulation of spinal GRK2 may be involved in the development and maintenance of persistent postoperative pain in rats following SMIR.

Key words: G protein- coupled receptor kinase 2; Pain, postoperative; Hyperalgesia; Spinal cord