髓核源性坐骨神经痛大鼠背根神经节磷酸化p38MAPK表达的变化

Expression of Phosphorylated p38MAPK in Sorsal Root Ganglion in Rats with Sciatica Caused by Nucleus Pulposus

【目的】观察髓核源性坐骨神经痛大鼠模型中背根神经节磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)表达的变化及其与炎性反应和机械痛敏的关系,以探讨腰椎间盘突出症的病理机制。【方法】选择成年SD雄性大鼠66只随机分为空白组(12只)、假手术组(18只)和模型组(36只)。模型组在左腰5神经背根神经节(L5DRG)自体髓核移植以建立大鼠非压迫性腰椎间盘突出模型,假手术组自体肌肉移植。空白组不进行手术。测量各组大鼠术前至术后21 d的左后肢50%机械性撤足阈值(50%PWT)以测定机械痛敏的变化,空白组、假手术组术后7 d及模型组术后7、14、21 d各12只大鼠取左腰5DRG用免疫组化法测定环氧化酶-2(COX-2)与p-p38MAPK的阳性细胞比率。【结果】假手术组50%PWT术后无明显变化,模型组术后7 d出现明显的50%PWT下降损伤,术后14 d达最低值,术后21 d部分恢复;空白组、假手术组术后7 dDRG的COX-2和p-p38MAPK微弱表达,模型组术后7 d DRG的COX-2和p-p38MAPK高表达,模型组术后14 d DRG的COX-2和p-p38MAPK表达更高,模型组术后21 d DRG的COX-2和p-p38MAPK表达减弱。【结论】背根神经节的p-p38MAPK的表达与非压迫性髓核所致炎性反应和坐骨神经病理性神经痛的变化密切相关。

[Objective] To observe the relationship of the expression of phosphorylated p38 mitogen activated protein kinase （p-p38MAPK） and the inflammatory reaction of dorsal root ganglion as well as sciatica caused by nucleus pulposus in rats. [Method] Sixty-six pathogen-free adult male Sprague-Dawley rats were randomly divided into three groups： naive group （n=12） and sham group （n=18） and model group （n=36）. Model group received left L5 hemilaminectomy and L5 dorsal root ganglion （DRG） epineuriumetomy as well as caudal vertebrae nucleus pulposus autograft, which establish an improved rat model of non- compressed lumbar intervertebral disc herniation. Sham groups received operation similar to model group except with muscles autograft. Naive group received no operation. 50% paw withdraw threshold （50%PWT） of left hind limb was measured 1 day before the surgery and on the 1^st, 3^rd, 7^th, 14^th and 21^st day after surgery in each group by ＂Up-Down＂ method to detect the change of the mechanical hyperalgsia. Twelve left L5 dorsal root ganglions were collected from naive group and sham group on the 7^th day after operation and model group on the 7^th, 14^th, and 21^st day after operation. Then the proportion of Cycloxygenase-2 （COX-2） and p- p38MAPK positive expression cell were detected by immunohistoehemistry method. [Results] The 50% PWT showed no change after operation in sham group. The 50% PWT in the model group decreased significantly from the first day to the 21^st day postoperation, The 50% PWT reached the lowest on the 14^th day and partially recovered on the 21^st day. The expression of COX-2 and p-p38MAPK in sham group and navie group were weak. In the 7^th day, the expression of COX-2 and p-p38MAPK was significantlyhigher in model group. In the 14^th day, the expression of COX-2 and p-p38MAPK continuously increased. In the 21^st day model group, the expression of COX-2 and p-p38MAPK significantly decreased. [Conclusion] p-p38MAPK expression in DRG correlated closely with the sciatica and the inflammatory reaction caused by nucleus pulposus.